Differential on and off durations for neurostimulation devices and methods

ABSTRACT

A device includes a handle, an expandable structure including a plurality of splines extending from a proximal hub to a distal hub, a first electrode on a first spline of the plurality of splines, an outer tube extending from the handle to the proximal hub, and a shaft extending through the outer tube from the handle to the distal hub. The expandable structure has a collapsed state and a self-expanded state. The handle is configured to retract the shaft. Retracting the shaft may expand the expandable structure outward of the self-expanded state.

INCORPORATION BY REFERENCE

This application is a continuation of U.S. patent application Ser. No.16/259,306, filed Jan. 28, 2019 and issued as U.S. Pat. No. 10,952,665,which is a continuation of U.S. patent application Ser. No. 15/892,199,filed Feb. 8, 2018 and issued as U.S. Pat. No. 10,188,343, which claimspriority benefit of U.S. Provisional Patent Application No. 62/464,039,filed Feb. 27, 2017, and which U.S. patent application Ser. No.15/892,199 is a continuation of PCT Application No. PCT/US2017/021214,filed Mar. 7, 2017, which claims priority benefit of each of U.S.Provisional Patent Application No. 62/305,988, filed Mar. 9, 2016, U.S.Provisional Patent Application No. 62/343,302, filed May 31, 2016, andU.S. Provisional Patent Application No. 62/464,039, filed Feb. 27, 2017,each of which is incorporated herein by reference in its entirety forall purposes. Any and all applications related thereto by way ofpriority thereto or therefrom are hereby incorporated by reference intheir entirety.

BACKGROUND Field

The present disclosure relates generally to methods and systems forfacilitating modulation (e.g., electrical neuromodulation), and moreparticularly to methods and systems for facilitating therapeutic andcalibration electrical neuromodulation of one or more nerves in andaround the heart.

Description of the Related Art

Acute heart failure is a cardiac condition in which a problem with thestructure or function of the heart impairs its ability to supplysufficient blood flow to meet the body's needs. The condition impairsquality of life and is a leading cause of hospitalizations and mortalityin the western world. Treating acute heart failure is typically aimed atremoval of precipitating causes, prevention of deterioration in cardiacfunction, and control of the patient's congestive state.

SUMMARY

Treatments for acute heart failure include the use of inotropic agents,such as dopamine and dobutamine. These agents, however, have bothchronotropic and inotropic effects and characteristically increase heartcontractility at the expense of significant increases in oxygenconsumption secondary to elevations in heart rate. As a result, althoughthese inotropic agents increase myocardial contractility and improvehemodynamics, clinical trials have consistently demonstrated excessmortality caused by cardiac arrhythmias and increase in myocardiumconsumption.

As such, there is a need for selectively and locally treating acuteheart failure and otherwise achieving hemodynamic control withoutcausing unwanted systemic effects. Accordingly, in some embodiments, noinotropics are used. In other embodiments, reduced dosages of inotropicsmay be used because, for example, synergistic effects are providedthrough various embodiments herein. By reducing the dosages, the sideeffects can also be significantly reduced.

Several embodiments of the present disclosure provide for methods oftissue modulation, such as neuromodulation, for cardiac and otherdisorders. For example, some embodiments provide methods and devices forneuromodulation of one or more nerves in and around a heart of apatient. Several methods of the present disclosure, for example, may beuseful in electrical neuromodulation of patients with cardiac disease,such as patients with acute or chronic cardiac disease. Several methodsof the present disclosure encompass, for example, neuromodulation of oneor more target sites of the autonomic nervous system of the heart. Insome embodiments, sensed non-electrical heart activity properties areused in making adjustments to one or more properties of the electricalneuromodulation delivered to the patient. Non-limiting examples ofmedical conditions that can be treated according to the presentdisclosure include cardiovascular medical conditions.

As discussed herein, the configuration of the catheter and electrodesystems of the present disclosure may advantageously allow for a portionof the catheter to be positioned within the vasculature of the patientin the main pulmonary artery and/or one or both of the pulmonaryarteries (the right pulmonary artery and the left pulmonary artery).Once positioned, the catheter and electrode systems of the presentdisclosure can provide electrical stimulation energy (e.g., electricalcurrent or electrical pulses) to stimulate the autonomic nerve fiberssurrounding the main pulmonary artery and/or one or both of thepulmonary arteries in an effort to provide adjuvant cardiac therapy tothe patient.

The catheter can include an elongate body having a first end and asecond end. The elongate body can include an elongate radial axis thatextends through the first end and the second end of the elongate body,and a first plane extends through the elongate radial axis. At least twoelongate stimulation members may extend from the elongate body, whereeach of the at least two elongate stimulation members curves into afirst volume defined at least in part by the first plane. In oneembodiment, at least one electrode is on each of the at least twoelongate stimulation members, where the at least one electrode form anelectrode array in the first volume. Conductive elements may extendthrough and/or along each of the elongate stimulation members, where theconductive elements conduct electrical current to combinations of two ormore of the electrodes in the electrode array.

In one embodiment, the at least two elongate stimulation members cancurve only in the first volume defined at least in part by the firstplane, and a second volume defined at least in part by the first planeand being opposite the first volume contains no electrodes. A secondplane can perpendicularly intersect the first plane along the elongateradial axis of the elongate body to divide the first volume into a firstquadrant volume and a second quadrant volume. The at least two elongatestimulation members can include a first elongate stimulation member anda second elongate stimulation member, where the first elongatestimulation member curves into the first quadrant volume and the secondelongate stimulation member curves into the second quadrant volume.

Each of the at least two elongate stimulation members can include astimulation member elongate body and a wire extending longitudinallythrough the elongate body and the stimulation member elongate body,where pressure applied by the wire against the stimulation memberelongate body at or near its distal end causes the wire to deflect,thereby imparting the curve into each of the at least two elongatestimulation members into the first volume defined at least in part bythe first plane. The catheter can also include an anchor member thatextends from the elongate body into a second volume defined at least inpart by the first plane and opposite the first volume, where the anchormember does not include an electrode.

In an additional embodiment, the catheter can also include a structureextending between at least two of the least two elongate stimulationmembers. An additional electrode can be positioned on the structure, theadditional electrode having a conductive element extending from theadditional electrode through one of the elongate stimulation members,where the conductive element conducts electrical current to combinationsof the additional electrode and at least one of the at least oneelectrode on each of the at least two elongate stimulation members. Anexample of such a structure is a mesh structure.

The catheter can also include a positioning gauge that includes anelongate gauge body with a first end and a bumper end distal to thefirst end. The elongate body of the catheter can include a first lumenthat extends from the first end through the second end of the elongatebody. The bumper end can have a shape with a surface area no less than asurface area of the distal end of the elongate body takenperpendicularly to the elongate radial axis, and the elongate gauge bodycan extend through the first lumen of the elongate body to position thebumper end beyond the second end of the elongate body. In oneembodiment, the first end of the positioning gauge extends from thefirst end of the elongate body, the elongate gauge body having a markingthat indicates a length between the second end of the elongate body andthe bumper end of the positioning gauge.

The present disclosure also includes a catheter system that includes acatheter and a pulmonary artery catheter having a lumen, where thecatheter extends through the lumen of the pulmonary artery catheter. Thepulmonary artery catheter can include an elongate catheter body with afirst end, a second end, a peripheral surface and an interior surface,opposite the peripheral surface, that defines the lumen extendingbetween the first end and the second end of the elongate catheter body.An inflatable balloon can be positioned on the peripheral surface of theelongate catheter body, the inflatable balloon having a balloon wallwith an interior surface that, along with a portion of the peripheralsurface of the elongate catheter body, defines a fluid tight volume. Aninflation lumen extends through the elongate catheter body, theinflation lumen having a first opening into the fluid tight volume ofthe inflatable balloon and a second opening proximal to the firstopening to allow for a fluid to move in and out of the fluid tightvolume to inflate and deflate the balloon.

The present disclosure also provides for a catheter that includes anelongate catheter body having a first end, a second end, a peripheralsurface and an interior surface defining an inflation lumen that extendsat least partially between the first end and the second end of theelongate catheter body; an inflatable balloon on the peripheral surfaceof the elongate catheter body, the inflatable balloon having a balloonwall with an interior surface that along with a portion of theperipheral surface of the elongate catheter body defines a fluid tightvolume, where the inflation lumen has a first opening into the fluidtight volume of the inflatable balloon and a second opening proximal tothe first opening to allow for a fluid to move in the volume to inflateand deflate the balloon; a plurality of electrodes positioned along theperipheral surface of the elongate catheter body, the plurality ofelectrodes located between the inflatable balloon and the first end ofthe elongate catheter body; conductive elements extending through theelongate catheter body, where the conductive elements conduct electricalcurrent to combinations of two or more of the at least one electrode ofthe plurality of electrodes; and a first anchor extending laterally fromthe peripheral surface of the elongate body, the first anchor havingstruts forming an open framework with a peripheral surface having alargest outer dimension greater than a largest outer dimension of theinflatable balloon.

In one embodiment, the first anchor is positioned between the inflatableballoon and the plurality of electrodes positioned along the peripheralsurface of the elongate catheter body. A portion of the elongatecatheter body that includes the plurality of electrodes can curve in apredefined radial direction when placed under longitudinal compression.In another embodiment, the first anchor is positioned between theplurality of electrodes positioned along the peripheral surface of theelongate catheter body and the first end of the elongate catheter body.

The elongate catheter body can also include a second interior surfacedefining a shaping lumen that extends from the first end towards thesecond end. A shaping wire having a first end and a second end can passthrough the shaping lumen with the first end of the shaping wireproximal to the first end of the elongate catheter body and the secondend of the shaping wire joined to the elongate catheter body so that theshaping wire imparts a curve into a portion of the elongate catheterbody having the plurality of electrodes when tension is applied to theshaping wire.

An embodiment of the catheter can also include an elongate catheter bodyhaving a first end, a second end, a peripheral surface and an interiorsurface defining an inflation lumen that extends at least partiallybetween the first end and the second end of the elongate catheter body;an inflatable balloon on the peripheral surface of the elongate catheterbody, the inflatable balloon having a balloon wall with an interiorsurface that along with a portion of the peripheral surface of theelongate catheter body defines a fluid tight volume, where the inflationlumen has a first opening into the fluid tight volume of the inflatableballoon and a second opening proximal to the first opening to allow fora fluid to move in the volume to inflate and deflate the balloon; afirst anchor extending laterally from the peripheral surface of theelongate catheter body the first anchor having struts forming an openframework with a peripheral surface having a diameter larger than adiameter of the inflatable balloon; an electrode catheter having anelectrode elongate body and a plurality of electrodes positioned along aperipheral surface of the electrode elongate body; conductive elementsextending through the electrode elongate body of the electrode catheter,where the conductive elements conduct electrical current to combinationstwo or more of the at least one electrode of the plurality ofelectrodes; and an attachment ring joined to the electrode catheter andpositioned around the peripheral surface of the elongate catheter bodyproximal to both the first anchor and the inflatable balloon.

A catheter system of the present disclosure can also include an elongatecatheter body having a first end, a second end, a peripheral surface andan interior surface defining an inflation lumen that extends at leastpartially between the first end and the second end of the elongatecatheter body, where the elongate catheter body includes an elongateradial axis that extends through the first end and the second end of theelongate body, and where a first plane extends through the elongateradial axis; an inflatable balloon on the peripheral surface of theelongate catheter body, the inflatable balloon having a balloon wallwith an interior surface that along with a portion of the peripheralsurface of the elongate catheter body defines a fluid tight volume,where the inflation lumen has a first opening into the fluid tightvolume of the inflatable balloon and a second opening proximal to thefirst opening to allow for a fluid to move in the volume to inflate anddeflate the balloon; an electrode cage having two or more ribs thatextend radially away from the peripheral surface of the elongatecatheter body towards the inflatable balloon, where the two or more ofthe ribs of the electrode cage curve into a first volume defined atleast in part by the first plane; one or more electrodes on each of theribs of the electrode cage, where the one or more electrodes on each ofthe rib form an electrode array in the first volume; conductive elementsextending through the two or more of the ribs of the electrode cage andthe elongate catheter body, where the conductive elements conductelectrical current to combinations of the one or more electrodes in theelectrode array; and an anchoring cage having two or more of the ribsthat extend radially away from the peripheral surface of the elongatecatheter body towards the inflatable balloon, where the two or more ofthe ribs of the anchoring cage curve into a second volume defined atleast in part by the first plane and being opposite the first volume,where the two or more of the rib of the anchoring cage do not include anelectrode.

In one example embodiment, a catheter includes an elongate body having afirst end and a second end. The elongate body includes a longitudinalcenter axis that extends between the first end and the second end. Theelongate body further includes three or more surfaces that define aconvex polygonal cross-sectional shape taken perpendicularly to thelongitudinal center axis. The catheter further includes one or more, butpreferably two or more, electrodes on one surface of the three or moresurfaces of the elongate body, where conductive elements extend throughthe elongate body. The conductive elements can conduct electricalcurrent to combinations of the one or more electrodes or in the instanceof a single electrode a second electrode is provided elsewhere in thesystem for flow of current. By way of example, the surfaces defining theconvex polygonal cross-sectional shape of the elongate body can be arectangle. Other shapes are possible. In one embodiment, the one or twoor more electrodes are only on the one surface of the three or moresurfaces of the elongate body. The one or more electrodes can have anexposed face that is co-planar with the one surface of the three or moresurfaces of the elongate body. The one surface of the three or moresurfaces of the elongate body can further include anchor structures thatextend above the one surface. In addition to the surfaces defining theconvex polygonal cross-sectional shape, the elongate body of thecatheter can also have a portion with a circular cross-section shapetaken perpendicularly to the longitudinal center axis. The catheter ofthis example embodiment can also include an inflatable balloon on aperipheral surface of the elongate body. The inflatable balloon includesa balloon wall with an interior surface that along with a portion of theperipheral surface of the elongate body defines a fluid tight volume. Aninflation lumen extends through the elongate body, the inflation lumenhaving a first opening into the fluid tight volume of the inflatableballoon and a second opening proximal to the first opening to allow fora fluid to move in the fluid tight volume to inflate and deflate theballoon.

In another example embodiment, a catheter includes an elongate bodyhaving a peripheral surface and a longitudinal center axis extendingbetween a first end and a second end. The elongate body of this exampleembodiment has an offset region defined by a series of predefined curvesalong the longitudinal center axis. The predefined curves include afirst portion having a first curve and a second curve in thelongitudinal center axis, a second portion following the first portion,where the second portion has a zero curvature (e.g., a straightportion), and a third portion following the second portion, the thirdportion having a third curve and a fourth curve. An inflatable balloonis positioned on the peripheral surface of the elongate body, theinflatable balloon having a balloon wall with an interior surface thatalong with a portion of the peripheral surface of the elongate bodydefines a fluid tight volume. An inflation lumen extends through theelongate body, the inflation lumen having a first opening into the fluidtight volume of the inflatable balloon and a second opening proximal tothe first opening to allow for a fluid to move in the fluid tight volumeto inflate and deflate the balloon. One or more electrodes arepositioned on the elongate body along the second portion of the offsetregion of the elongate body. Conductive elements extend through theelongate body, where the conductive elements conduct electrical currentto combinations of the one or more electrodes. The portions of theelongate body of this example embodiment of a catheter can have avariety of shapes. For example, the second portion of the elongate bodycan form a portion of a helix. The elongate body can also have three ormore surfaces defining a convex polygonal cross-sectional shape takenperpendicularly to the longitudinal center axis, where the one or moreelectrodes are on one surface of the three or more surfaces of theelongate body. For this embodiment, the convex polygonal cross-sectionalshape can be a rectangle. The one or more electrodes are only on the onesurface of the three or more surfaces of the elongate body. The one ormore electrodes can have an exposed face that is co-planar with the onesurface of the three or more surfaces of the elongate body.

In another example embodiment, a catheter includes an elongate body witha peripheral surface and a longitudinal center axis extending between afirst end and a second end. The elongate body includes a surfacedefining a deflection lumen, where the deflection lumen includes a firstopening and a second opening in the elongate body. An inflatable balloonis located on the peripheral surface of the elongate body, theinflatable balloon having a balloon wall with an interior surface thatalong with a portion of the peripheral surface of the elongate bodydefines a fluid tight volume. An inflation lumen extends through theelongate body, the inflation lumen having a first opening into the fluidtight volume of the inflatable balloon and a second opening proximal tothe first opening to allow for a fluid to move in the fluid tight volumeto inflate and deflate the balloon. One or more electrodes are locatedon the elongate body, where the second opening of the deflection lumenis opposite the one or more electrodes on the elongate body. Conductiveelements extend through the elongate body, where the conductive elementsconduct electrical current to combinations of the one or moreelectrodes. The catheter also includes an elongate deflection member,where the elongate deflection member extends through the second openingof the deflection lumen in a direction opposite the one or moreelectrodes on one surface of the elongate body.

In another example embodiment, a catheter includes an elongate bodyhaving a peripheral surface and a longitudinal center axis extendingbetween a first end and a second end. The elongate body includes asurface defining an electrode lumen, where the electrode lumen includesa first opening in the elongate body. The catheter further includes aninflatable balloon on the peripheral surface of the elongate body, theinflatable balloon having a balloon wall with an interior surface thatalong with a portion of the peripheral surface of the elongate bodydefines a fluid tight volume. An inflation lumen extends through theelongate body, the inflation lumen having a first opening into the fluidtight volume of the inflatable balloon and a second opening proximal tothe first opening to allow for a fluid to move in the fluid tight volumeto inflate and deflate the balloon. The catheter further includes anelongate electrode member, where the elongate electrode member extendsthrough the first opening of the electrode lumen of the elongate body,where the electrode member includes one or more electrodes andconductive elements extending through the electrode lumen, where theconductive elements conduct electrical current to combinations of theone or more electrodes. The elongate electrode member can form a loopthat extends away from the peripheral surface of the elongate body. Theelongate electrode member forming the loop can be in a plane that isco-linear with the longitudinal center axis of the elongate body.Alternatively, the elongate electrode member forming the loop is in aplane that is perpendicular to the longitudinal center axis of theelongate body.

According to some methods of the present disclosure and as will bediscussed more fully herein, a catheter having an electrode array isinserted into the pulmonary trunk and positioned at a location such thatthe electrode array is positioned with its electrodes in contact withthe posterior surface, the superior surface and/or the inferior surfaceof the right pulmonary artery. From this location, electrical currentcan be delivered to or from the electrode array to selectively modulatethe autonomic nervous system of the heart. For example, electricalcurrent can be delivered to or from the electrode array to selectivelymodulate the autonomic cardiopulmonary nerves of the autonomic nervoussystem, which can modulate heart contractility more than heart rate.Preferably, the electrode array is positioned at a site along theposterior wall and/or superior wall of the right pulmonary artery suchthat the electrical current delivered to or from the electrode arrayresults in the greatest effect on heart contractility and the leasteffect on heart rate and/or oxygen consumption compared to electricalcurrent delivered at other sites in the right pulmonary artery and/orleft pulmonary artery. In certain embodiments, the effect on heartcontractility is to increase heart contractility.

As used herein, the electrical current delivered to or from theelectrode array can be in the form of a time variant electrical current.Preferably such a time variant electrical current can be in the form ofone or more of a pulse of electrical current (e.g., at least one pulseof electrical current), one or more of waveform, such as a continuouswave of electrical current, or a combination thereof.

As discussed herein, the present disclosure provides for a method fortreating a patient having a heart with a pulmonary trunk. Portions ofthe pulmonary trunk can be defined with a right lateral plane thatpasses along a right luminal surface of the pulmonary trunk, a leftlateral plane parallel with the right lateral plane, where the leftlateral plane passes along a left luminal surface of the pulmonarytrunk. The right lateral plane and the left lateral plane extend in adirection that generally aligns with the posterior and anteriordirections of a subject's (e.g., patient's) body. A branch point ispositioned between the right lateral plane and the left lateral plane,where the branch point helps to define the beginning of a left pulmonaryartery and a right pulmonary artery of the heart. The method furtherincludes moving a catheter having an electrode array through thepulmonary trunk towards the branch point, where the electrode arrayincludes one or more, preferably two or more, electrodes. The electrodearray is positioned in the right pulmonary artery to the right of theleft lateral plane, where the one or more electrodes contacts aposterior surface, a superior surface and/or an inferior surface of theright pulmonary artery to the right of the left lateral plane. In anadditional embodiment, the electrode array can be positioned in theright pulmonary artery to the right of the right lateral plane, wherethe one or more electrodes contacts the posterior surface, the superiorsurface and/or the inferior surface of the right pulmonary artery to theright of the right lateral plane. This example embodiment of a methodfurther includes contacting the one or more electrodes on the posteriorsurface, the superior surface and/or the inferior surface of the rightpulmonary artery at a position superior to (e.g., situated above) thebranch point. The at least a portion of the catheter can also bepositioned in contact with a portion of the surface defining the branchpoint. In this embodiment, the portion of the catheter can be providedwith a shape that provides an increase in surface area that can help tohold the portion of the catheter against the branch point.

In an additional embodiment, the pulmonary trunk has a diameter takenacross a plane perpendicular to both the left lateral plane and theright lateral plane, where the electrode array is positioned in theright pulmonary artery to extend from a point to the right of the leftlateral plane to a point about three times the diameter of the pulmonarytrunk to the right of the branch point. The right pulmonary artery canalso include a branch point that divides the right pulmonary artery intoat least two additional arteries that are distal to the branch pointhelping to define the beginning of the left pulmonary artery and theright pulmonary artery. The electrode array can be positioned in theright pulmonary artery between the branch point helping to define thebeginning of the left pulmonary artery and the right pulmonary arteryand the branch point that divides the right pulmonary artery into atleast two additional arteries. Once in position, electrical current canbe provided from or to the one or more electrodes of the electrodearray. A value of a cardiac parameter of the patient can be measured inresponse to the electrical current from or to the one or more electrodesof the electrode array. From the value of the cardiac parameter, changescan be made to which of the electrodes are used to provide theelectrical current in response to the value of the cardiac parameter.Changes can also be made to the nature of the electrical currentprovided in response to the value of the cardiac parameter. Such changesinclude, but are not limited to, changes in voltage, amperage, waveform,frequency and pulse width, by way of example. In addition, theelectrodes of the one or more electrodes on the posterior surface, thesuperior surface and/or the inferior surface of the right pulmonaryartery can be moved in response to the values of the cardiac parameter.The electrical current provided to or from the one or more electrodes ofthe electrode array can be provided as at least one pulse of electricalcurrent to or from the one or more electrodes of the electrode array.Examples of such a cardiac parameter include, but are not limited to,measuring a pressure parameter, an acoustic parameter, an accelerationparameter and/or an electrical parameter (e.g., ECG) of the heart of thepatient as the cardiac parameter.

Several methods of the present disclosure allow for electricalneuromodulation of the heart of the patient, for example includingdelivering one or more electrical pulses through a catheter positionedin a pulmonary artery of the heart of the patient, sensing from at leasta first sensor positioned at a first location within the vasculature ofthe heart one or more heart activity properties (e.g., a non-electricalheart activity property) in response to the one or more electricalpulses, and adjusting a property of the one or more electrical pulsesdelivered through the catheter positioned in the pulmonary artery of theheart in response to the one or more heart activity properties. Themethods may provide adjuvant cardiac therapy to the patient.

Sensing from at least the first sensor positioned at the first locationcan include sensing one or more of a pressure property, an accelerationproperty, an acoustic property, a temperature, and a blood chemistryproperty from within the vasculature of the heart. Among otherlocations, the first sensor can be positioned in one of a left pulmonaryartery, a right pulmonary artery, a pulmonary artery branch vessel, or apulmonary trunk of the heart. The one or more electrical pulses canoptionally be delivered through the catheter positioned in one of theleft pulmonary artery, the right pulmonary artery, or pulmonary trunk ofthe heart that does not contain the first sensor. The first sensor canalso be positioned in a pulmonary trunk of the heart.

Other locations for the first sensor can include in the right ventricleof the heart and in the right atrium of the heart. When positioned inthe right atrium of the heart, the first sensor can optionally bepositioned on the septal wall of the right atrium of the heart. Thefirst sensor could also be positioned on the septal wall of the rightventricle. The right ventricle and the left ventricle share a septalwall, so a sensor in the right ventricle or on the septal wall of theright ventricle may be preferable for detecting properties indicative ofleft ventricle contractility or cardiac output. Additional locations forpositioning the first sensor include in a superior vena cava of theheart, the inferior vena cava of the heart, and in a coronary sinus ofthe heart. When positioned in the coronary sinus of the heart, the firstsensor can be used to sense at least one of a temperature or a bloodoxygen level.

In some embodiments, the first sensor may be positioned in the leftatrium (e.g., by forming an aperture in the septal wall between theright atrium and the left atrium, or by using a patent foramen ovale(PFO) or atrial septal defect (ASD)). A sensor in the left atrium may beuseful for detecting properties indicative of the left ventricle. If theleft atrium has been accessed, in some embodiments, the sensor may bepositioned in the left ventricle itself, which may provide the mostdirect measurement of properties associated with the left ventricle. Insome embodiments, the sensor may be positioned downstream of the leftventricle, including the aorta, aortic branch arteries, etc. When theprocedure is complete, any aperture that was created or existing may beclosed using a closure device such as Amplatzer, Helex, CardioSEAL, orothers.

Some methods can include sensing one or more cardiac properties from askin surface of the patient, and adjusting the property of the one ormore electrical pulses delivered through the catheter positioned in thepulmonary artery of the heart in response to the one or more heartactivity properties (e.g., non-electrical properties) from the firstsensor positioned at a first location within the vasculature of theheart and/or the one or more cardiac properties from the skin surface ofthe patient. The one or more cardiac properties sensed from the skinsurface of the patient can include, for example, an electrocardiogramproperty.

Some methods can include sensing from at least a second sensorpositioned at a second location within the vasculature of the heart oneor more heart activity properties (e.g., non-electrical heart activityproperties) in response to the one or more electrical pulses, andadjusting the property of the one or more electrical pulses deliveredthrough the catheter positioned in the pulmonary artery of the heart inresponse to the one or more heart activity properties from the firstsensor and/or the one or more heart activity properties from the secondsensor.

Adjusting the property of the one or more electrical pulses can includea variety of responses. For example, adjusting the property of the oneor more electrical pulses can include changing which of an electrode orplurality of electrodes on the catheter is used to deliver the one ormore electrical pulses. For another example, adjusting the property ofthe one or more electrical pulses can include moving the catheter toreposition one or more electrodes of the catheter in the pulmonaryartery of the heart. For yet another example, adjusting the property ofthe one or more electrical pulses can include changing at least one ofan electrode polarity, a pulsing mode, a pulse width, an amplitude, afrequency, a phase, a voltage, a current, a duration, an inter-pulseinterval, a duty cycle, a dwell time, a sequence, a wavelength, and/or awaveform of the one or more electrical pulses.

A hierarchy of electrode configurations can be assigned from which todeliver the one or more electrical pulses. The one or more electricalpulses can be delivered based on the hierarchy of electrodeconfigurations, where the one or more heart activity properties sensedin response to the one or more electrical pulses can be analyzed and anelectrode configuration can be selected to use for delivering the one ormore electrical pulses through the catheter positioned in the pulmonaryartery of a heart of a patient based on the analysis. A hierarchy can beassigned to each property of the one or more electrical pulses deliveredthrough the catheter positioned in the pulmonary artery of the heart,where the one or more electrical pulses are delivered based on thehierarchy of each property. The one or more non-electrical heartactivity properties sensed in response to the one or more electricalpulses are analyzed and an electrode configuration can be selected to beused for delivering the one or more electrical pulses through thecatheter positioned in the pulmonary artery of a heart of a patientbased on the analysis. Analyzing the one or more heart activityproperties can include analyzing a predetermined number of the one ormore heart activity properties.

In some embodiments, a method of facilitating therapeuticneuromodulation of a heart of a patient comprises positioning anelectrode in a pulmonary artery of a heart and positioning a sensor in aright ventricle of the heart. The method further comprises delivering,via a stimulation system, a first series of electrical signals to theelectrode. The first series comprises a first plurality of electricalsignals. Each of the first plurality of electrical signals comprises aplurality of parameters. Each of the first plurality of electricalsignals of the first series only differs from one another by a magnitudeof a first parameter of the plurality of parameters. The method furthercomprises, after delivering the first series of electrical signals tothe electrode, delivering, via the stimulation system, a second seriesof electrical signals to the electrode. The second series comprises asecond plurality of electrical signals. Each of the second plurality ofelectrical signals comprises the plurality of parameters. Each of thesecond plurality of electrical signals of the second series only differsfrom one another by a magnitude of a second parameter of the pluralityof parameters. The second parameter is different than the firstparameter. The method further comprises determining, via the sensor,sensor data indicative of one or more non-electrical heart activityproperties in response to delivering the first series of electricalsignals and the second series of electrical signals, and delivering atherapeutic neuromodulation signal to the pulmonary artery usingselected electrical parameters. The selected electrical parameterscomprise a selected magnitude of the first parameter and a selectedmagnitude of the second parameter. The selected magnitudes of the firstand second parameters are based at least partially on the sensor data.The therapeutic neuromodulation signal increases heart contractilitymore than heart rate.

The method may further comprise delivering, via the stimulation system,a third series of electrical signals to the electrode. The third seriescomprises a third plurality of electrical signals. Each of the thirdplurality of electrical signals comprises the plurality of parameters.Each of the third plurality of electrical signals of the third seriesonly differs from one another by a magnitude of a third parameter of theplurality of parameters. The third parameter is different than the firstparameter and the second parameter. The method may further comprisedetermining, via the sensor, sensor data indicative of the one or morenon-electrical heart activity properties in response to delivering thethird series of electrical signals. The selected electrical parametersmay comprise a selected magnitude of the third parameter. The selectedmagnitude of the third parameter is based at least partially on thesensor data.

The method may further comprise determining a desired hierarchy betweenthe first series and the second series. The pulmonary artery maycomprise a right pulmonary artery. The one or more non-electrical heartactivity properties may comprise at least one of a pressure property, anacceleration property, an acoustic property, a temperature, and a bloodchemistry property. Determining the sensor data may comprisedetermining, via a second sensor on a skin surface, sensor dataindicative of an electrocardiogram property in response to deliveringthe first series of electrical signals and the second series ofelectrical signals.

The first parameter may be one of the following: a polarity, a pulsingmode, a pulse width, an amplitude, a frequency, a phase, a voltage, acurrent, a duration, an inter-pulse interval, a duty cycle, a dwelltime, a sequence, a wavelength, a waveform, or an electrode combination,and, optionally, the second parameter may be a different one of thefollowing: a polarity, a pulsing mode, a pulse width, an amplitude, afrequency, a phase, a voltage, a current, a duration, an inter-pulseinterval, a duty cycle, a dwell time, a sequence, a wavelength, awaveform, or an electrode combination. The second parameter may be oneof the following: a polarity, a pulsing mode, a pulse width, anamplitude, a frequency, a phase, a voltage, a current, a duration, aninter-pulse interval, a duty cycle, a dwell time, a sequence, awavelength, a waveform, or an electrode combination. The first parametermay comprise current and the second parameter may comprise a parameterrelating to timing (e.g., one of frequency and duty cycle).

In some embodiments, a method of facilitating therapeuticneuromodulation of a heart of a patient comprises positioning anelectrode in a pulmonary artery of a heart, positioning a sensor in aright ventricle of the heart, delivering, via a stimulation system, afirst electrical signal of a series of electrical signals to theelectrode, and, after delivering the first electrical signal,delivering, via the stimulation system, a second electrical signal ofthe series of electrical signals to the electrode. The second electricalsignal differs from the first electrical signal by a magnitude of afirst parameter of a plurality of parameters. The method furthercomprises determining, via the sensor, sensor data indicative of one ormore non-electrical heart activity properties in response to thedelivery of the series of electrical signals, and delivering atherapeutic neuromodulation signal to the pulmonary artery usingselected electrical parameters. The selected electrical parameterscomprise a selected magnitude of the first parameter. The selectedmagnitude of the first parameter is based at least partially on thesensor data. The therapeutic neuromodulation signal increases heartcontractility more than heart rate.

The pulmonary artery may comprise a right pulmonary artery. Thepulmonary artery may comprise a left pulmonary artery. The pulmonaryartery may comprise a pulmonary trunk. The one or more non-electricalheart activity properties may comprise at least one of a pressureproperty, an acceleration property, an acoustic property, a temperature,and a blood chemistry property. Determining the sensor data may comprisedetermining, via a second sensor on a skin surface of the patient,sensor data indicative of an electrocardiogram property in response todelivering the series of electrical signals. The first parameter may beone of the following: a polarity, a pulsing mode, a pulse width, anamplitude, a frequency, a phase, a voltage, a current, a duration, aninter-pulse interval, a duty cycle, a dwell time, a sequence, awavelength, a waveform, or an electrode combination.

In some embodiments, a method of facilitating therapeuticneuromodulation of a heart of a patient comprises delivering a firstseries of electrical signals to an electrode in a first anatomicallocation, and, after delivering the first series of electrical signalsto the electrode, delivering a second series of electrical signals tothe electrode. The first series comprises a first plurality ofelectrical signals. Each of the first plurality of electrical signalscomprises a plurality of parameters. Each of the first plurality ofelectrical signals of the first series only differs from one another bya magnitude of a first parameter of the plurality of parameters. Thesecond series comprises a second plurality of electrical signals. Eachof the second plurality of electrical signals comprises the plurality ofparameters. Each of the second plurality of electrical signals of thesecond series only differs from one another by a magnitude of a secondparameter of the plurality of parameters. The second parameter isdifferent than the first parameter. The method further comprisessensing, via a sensor in a second anatomical location different than thefirst anatomical location, sensor data indicative of one or morenon-electrical heart activity properties in response to delivering thefirst series of electrical signals and the second series of electricalsignals, and providing a therapeutic neuromodulation signal to the firstanatomical location using selected electrical parameters. The selectedelectrical parameters comprise a selected magnitude of the firstparameter and a selected magnitude of the second parameter. The selectedmagnitudes of the first and second parameters are based at leastpartially on the sensor data. The therapeutic neuromodulation signalincreases heart contractility.

The method may further comprise delivering a third series of electricalsignals to the electrode. The third series comprises a third pluralityof electrical signals. Each of the third plurality of electrical signalscomprises the plurality of parameters. Each of the third plurality ofelectrical signals of the third series only differs from one another bya magnitude of a third parameter of the plurality of parameters. Thethird parameter is different than the first parameter and the secondparameter. The method may further comprise sensing, via the sensor,sensor data indicative of the one or more non-electrical heart activityproperties in response to delivering the third series of electricalsignals. The selected electrical parameters may comprise a selectedmagnitude of the third parameter. The selected magnitude of the thirdparameter is based at least partially on the sensor data.

The method may further comprise determining a desired hierarchy betweenthe first series and the second series. The first anatomical locationmay comprise a right pulmonary artery. The pulmonary artery may comprisea left pulmonary artery. The pulmonary artery may comprise a pulmonarytrunk. The one or more non-electrical heart activity properties maycomprise at least one of a pressure property, an acceleration property,an acoustic property, a temperature, and a blood chemistry property.Sensing the sensor data may comprise determining, via a second sensor ona skin surface, sensor data indicative of an electrocardiogram propertyin response to delivering the first series of electrical signals and thesecond series of electrical signals.

The first parameter may one of the following: a polarity, a pulsingmode, a pulse width, an amplitude, a frequency, a phase, a voltage, acurrent, a duration, an inter-pulse interval, a duty cycle, a dwelltime, a sequence, a wavelength, a waveform, or an electrode combination,and, optionally, the second parameter may be a different one of thefollowing: a polarity, a pulsing mode, a pulse width, an amplitude, afrequency, a phase, a voltage, a current, a duration, an inter-pulseinterval, a duty cycle, a dwell time, a sequence, a wavelength, awaveform, or an electrode combination. The second parameter may one ofthe following: a polarity, a pulsing mode, a pulse width, an amplitude,a frequency, a phase, a voltage, a current, a duration, an inter-pulseinterval, a duty cycle, a dwell time, a sequence, a wavelength, awaveform, or an electrode combination. The first parameter may comprisecurrent and the second parameter may comprise a parameter related totiming (e.g., one of frequency and duty cycle).

In some embodiments, a method of facilitating therapeuticneuromodulation of a heart of a patient comprises delivering a firstelectrical signal of a series of electrical signals to an electrode in afirst anatomical location, and, after delivering the first electricalsignal, delivering a second electrical signal of the series ofelectrical signals to the electrode. The second electrical signaldiffers from the first electrical signal by a magnitude of a firstparameter of a plurality of parameters. The method further comprisessensing, via a sensor in a second anatomical location different than thefirst anatomical location, sensor data indicative of one or morenon-electrical heart activity properties in response to the delivery ofthe series of electrical signals, and providing a therapeuticneuromodulation signal to the first anatomical location using selectedelectrical parameters. The selected electrical parameters comprise aselected magnitude of the first parameter. The selected magnitude of thefirst parameter is based at least partially on the sensor data. Thetherapeutic neuromodulation signal increases heart contractility.

The first anatomical location may comprise a right pulmonary artery. Thefirst anatomical location may comprise a left pulmonary artery. Thefirst anatomical location may comprise a pulmonary trunk. The one ormore non-electrical heart activity properties may comprise at least oneof a pressure property, an acceleration property, an acoustic property,a temperature, and a blood chemistry property. Sensing the sensor datamay comprise sensing, via a second sensor on a skin surface of thepatient, sensor data indicative of an electrocardiogram property inresponse to delivering the series of electrical signals. The firstparameter may be one of the following: a polarity, a pulsing mode, apulse width, an amplitude, a frequency, a phase, a voltage, a current, aduration, an inter-pulse interval, a duty cycle, a dwell time, asequence, a wavelength, a waveform, or an electrode combination.

In some embodiments, a neuromodulation system for facilitating deliveryof electric signals to a heart of a patient comprises a catheter and astimulation system. The catheter comprises a catheter body comprising aproximal end, a distal end, a lumen extending from the proximal endtowards the distal end, and an outer surface. The catheter furthercomprises an electrode on the outer surface. The electrode is configuredto deliver an electrical signal to a pulmonary artery of a patient. Thecatheter further comprises a sensor on the outer surface. The sensor isconfigured to sense a heart activity property from a location within invasculature of the patient. The stimulation system comprises a pulsegenerator configured to deliver a first series of electrical signals anda second series of electrical signals to the electrode. The first seriescomprises a first plurality of electrical signals. Each of the firstplurality of electrical signals comprises a plurality of parameters.Each of the first plurality of electrical signals of the first seriesonly differs from one another by a magnitude of a first parameter of theplurality of parameters. The second series comprises a second pluralityof electrical signals. Each of the second plurality of electricalsignals comprises the plurality of parameters. Each of the secondplurality of electrical signals of the second series only differs fromone another by a magnitude of a second parameter of the plurality ofparameters. The second parameter is different than the first parameter.The stimulation system further comprises a non-transitorycomputer-readable medium configured to store sensor data indicative ofone or more non-electrical heart activity properties in response todelivering the first series of electrical signals and the second seriesof electrical signals to the electrode, and a processor configured todetermine a selected magnitude of the first parameter and a selectedmagnitude of the second parameter based at least partially on the sensordata. The non-transitory computer readable medium is configured to storeselected electrical parameters including the selected magnitude of thefirst parameter and the selected magnitude of the second parameter. Thepulse generator is configured to deliver a therapeutic neuromodulationsignal to the electrode using selected electrical parameters.

In some embodiments, a neuromodulation system for facilitatingdelivery/of electric signals to a heart of a patient comprises acatheter and a stimulation system. The catheter comprises a catheterbody comprising a proximal end, a distal end, a lumen extending from theproximal end towards the distal end, and an outer surface. The catheterfurther comprises an electrode on the outer surface. The electrode isconfigured to deliver an electrical signal to a pulmonary artery of apatient. The catheter further comprises a sensor on the outer surface.The sensor is configured to sense a heart activity property from alocation within in vasculature of the patient. The stimulation systemcomprises a pulse generator configured to deliver a series of electricalsignals to the electrode. The series comprises a first electrical signaland a second electrical signal. The second electrical signal differsfrom the first electrical signal by a magnitude of a first parameter ofa plurality of parameters. The stimulation system further comprises anon-transitory computer-readable medium configured to store sensor dataindicative of one or more non-electrical heart activity properties inresponse to delivering the series of electrical signals to theelectrode, and a processor configured to determine a selected magnitudeof the first parameter based at least partially on the sensor data. Thenon-transitory computer readable medium is configured to store selectedelectrical parameters including the selected magnitude of the firstparameter. The pulse generator is configured to deliver a therapeuticneuromodulation signal to the electrode using selected electricalparameters.

In some embodiments, a neuromodulation system for facilitating deliveryof electric signals to a heart of a patient comprises a catheter and ashaping wire. The catheter comprises a catheter body comprising aproximal end, a distal end, a lumen extending from the proximal endtowards the distal end, and an outer surface. The catheter furthercomprises an electrode on the outer surface. The electrode is configuredto deliver an electrical signal to a pulmonary artery of a patient. Theshaping wire is configured to be positioned in the lumen of the catheterbody. The shaping wire comprises a bent portion. When the shaping wireis inserted in the lumen of the catheter body, the catheter bodycomprises a curved portion corresponding to the bent portion of theshaping wire.

The heart activity property may comprise a non-electrical heartyactivity property. The non-electrical heart activity property maycomprise at least one of a pressure property, an acceleration property,an acoustic property, a temperature, and a blood chemistry property. Theelectrode may be configured to deliver the electrical signal to a rightpulmonary artery of the patient. The electrode may be configured to bepositioned in a different location than the sensor. The catheter systemmay comprise a plurality of electrodes including the electrode. Thelocation may be a pulmonary trunk, a right ventricle, a septal wall of aright ventricle, a right atrium, a septal wall of a right atrium, asuperior vena cava, a pulmonary branch artery vessel, an inferior venacava, or a coronary sinus. The neuromodulation system may furthercomprise a skin sensor configured to sense a cardiac property from askin surface of the patient. The heart activity property may comprise anon-electrical heart activity property and wherein the cardiac propertymay comprise an electrical cardiac property. The electrical cardiacproperty may comprise an electrocardiogram property.

In some embodiments, a method of neuromodulation of a heart of a patientcomprises positioning a catheter including an electrode in a pulmonaryartery of a heart, positioning a sensor in a location within vasculatureof the heart, delivering, via a stimulation system, a first set of oneor more electrical pulses to the electrode, the first set of one or moreelectrical pulses having a first pulse property, and, after deliveringthe first delivering set of one or more electrical pulses to theelectrode, delivering, via the stimulation system, a second set of oneor more electrical pulses to the electrode. The second set of one ormore electrical pulses has a second pulse property different than thefirst pulse property. The method further comprises deliveringtherapeutic electrical pulses to the pulmonary artery using an electrodeconfiguration selected by analyzing one or more heart activityproperties sensed, via the sensor, in response to the delivery of thefirst and second sets of electrical pulses. The electrode configurationcomprises the first pulse property or the second pulse property based atleast partially on the analysis. The therapeutic neuromodulation signalincreases heart contractility more than heart rate.

In some embodiments, a method of modulation (e.g., electricalneuromodulation) of a heart of a patient comprises delivering one ormore electrical pulses through a catheter positioned in a pulmonaryartery of the heart of the patient, sensing from at least a first sensorpositioned at a first location within a vasculature of the heart one ormore non-electrical heart activity properties in response to the one ormore electrical pulses, and adjusting a property of the one or moreelectrical pulses delivered through the catheter positioned in thepulmonary artery of the heart in response to the one or morenon-electrical heart activity properties.

In some embodiments, sensing from at least the first sensor positionedat the first location may include sensing one or more of a pressureproperty, an acceleration property, an acoustic property, a temperature,and a blood chemistry property from within the vasculature of the heart.

In one embodiment, a first sensor is placed in one of a left pulmonaryartery, a right pulmonary artery, or a pulmonary trunk of the heart. Oneor more electrical pulses are delivered through the catheter positionedin one of the left pulmonary artery, the right pulmonary artery, or thepulmonary trunk of the heart that does not contain the first sensor.

The first sensor may be positioned in the left pulmonary artery. Thefirst sensor may be positioned in the right pulmonary artery. The firstsensor may be positioned in other vessels in and around the heart,including, but not limited to, the pulmonary trunk, a pulmonary arterybranch vessel, right ventricle, a septal wall of the right ventricle, aright atrium, the septal wall of the right atrium, a superior vena cava,an inferior vena cava or a coronary sinus The first sensor (e.g., in thecoronary sinus) may sense at least one of a temperature or a bloodoxygen level.

In several embodiments, the method may include sensing one or morecardiac properties from a skin surface of the patient and adjusting theproperty of the one or more electrical pulses delivered through thecatheter positioned in the pulmonary artery of the heart in response tothe one or more non-electrical heart activity properties and the one ormore cardiac properties from the skin surface of the patient. The one ormore cardiac properties sensed from the skin surface of the patient mayinclude an electrocardiogram property. The may include sensing from atleast a second sensor positioned at a second location within thevasculature of the heart one or more non-electrical heart activityproperties in response to the one or more electrical pulses andadjusting the property of the one or more electrical pulses deliveredthrough the catheter positioned in the pulmonary artery of the heart inresponse to the one or more non-electrical heart activity propertiesreceived by the first sensor and the second sensor. In severalembodiments, adjusting the property of the one or more electrical pulsesmay include one or more of the following (i) changing which electrode onthe catheter is used to deliver the one or more electrical pulses; (ii)moving the catheter to reposition electrodes of the catheter in thepulmonary artery of the heart; (iii) changing at least one of anelectrode polarity, a pulsing mode, a pulse width, an amplitude, afrequency, a phase, a voltage, a current, a duration, an inter-pulseinterval, a duty cycle, a dwell time, a sequence, a wavelength, awaveform, or an electrode combination of the one or more electricalpulses.

In several embodiments, the method may include assigning a hierarchy ofelectrode configurations from which to deliver the one or moreelectrical pulses, delivering the one or more electrical pulses based atleast partially on the hierarchy of electrode configurations, analyzingthe one or more non-electrical heart activity properties sensed inresponse to the one or more electrical pulses, and selecting anelectrode configuration to use for delivering the one or more electricalpulses through the catheter positioned in the pulmonary artery of aheart of a patient based at least partially on the analysis. The methodmay include assigning a hierarchy to each property of the one or moreelectrical pulses delivered through the catheter positioned in thepulmonary artery of the heart, delivering the one or more electricalpulses based at least partially on the hierarchy of each property,analyzing the one or more non-electrical heart activity propertiessensed in response to the one or more electrical pulses, and selectingan electrode configuration to use for delivering the one or moreelectrical pulses through the catheter positioned in the pulmonaryartery of a heart of a patient based at least partially on the analysis.Analyzing the one or more non-electrical heart activity properties mayinclude analyzing a predetermined number of the one or morenon-electrical heart activity properties.

In several embodiments, therapeutic neuromodulation is not provided.Instead, several embodiments are provided for the purposes ofcalibrating or optimizing a signal for, e.g., diagnosis or calibrationpurposes.

In some embodiments, a method of non-therapeutic calibration comprisespositioning an electrode in a pulmonary artery of a heart andpositioning a sensor in a right ventricle of the heart. The systemfurther comprises delivering, via a stimulation system, a first seriesof electrical signals to the electrode. The first series comprises afirst plurality of electrical signals. Each of the first plurality ofelectrical signals comprises a plurality of parameters. Each of thefirst plurality of electrical signals of the first series only differsfrom one another by a magnitude of a first parameter of the plurality ofparameters. The method further comprises, after delivering the firstseries of electrical signals to the electrode, delivering, via thestimulation system, a second series of electrical signals to theelectrode. The second series comprises a second plurality of electricalsignals. Each of the second plurality of electrical signals comprisesthe plurality of parameters. Each of the second plurality of electricalsignals of the second series only differs from one another by amagnitude of a second parameter of the plurality of parameters. Thesecond parameter is different than the first parameter. The methodfurther comprises determining, via the sensor, sensor data indicative ofone or more non-electrical heart activity properties in response todelivering the first series of electrical signals and the second seriesof electrical signals. The method further comprises determining atherapeutic neuromodulation signal to be delivered to the pulmonaryartery using selected electrical parameters. The selected electricalparameters comprise a selected magnitude of the first parameter and aselected magnitude of the second parameter. The selected magnitudes ofthe first and second parameters are based at least partially on thesensor data.

In some embodiments, a method of non-therapeutic calibration comprisesdelivering a first electrical signal of a series of electrical signalsto an electrode in a first anatomical location and, after delivering thefirst electrical signal, delivering a second electrical signal of theseries of electrical signals to the electrode. The second electricalsignal differs from the first electrical signal by a magnitude of afirst parameter of a plurality of parameters. The method furthercomprises sensing, via a sensor in a second anatomical locationdifferent than the first anatomical location, sensor data indicative ofone or more non-electrical heart activity properties in response to thedelivery of the series of electrical signals, and determining atherapeutic neuromodulation signal to be delivered to the firstanatomical location using selected electrical parameters. The selectedelectrical parameters comprise a selected magnitude of the firstparameter. The selected magnitude of the first parameter is based atleast partially on the sensor data.

In some embodiments, a device comprises or consists essentially of afirst part and a second part. The first part comprises a first annularportion having a first diameter and a first plurality of splinesextending distally from the first annular portion. The second partcomprises a second annular portion having a second diameter and a secondplurality of splines extending distally and radially outward from thesecond annular portion. The second diameter is less than the firstdiameter. The second annular portion is telescopeable in the firstannular portion. Each of the first plurality of splines is coupled toone spline of the second plurality of splines. Upon distal longitudinaladvancement of the second part relative to the first part, the firstpart expands from a collapsed state to an expanded state. The firstplurality of splines is circumferentially spaced in the expanded state.Upon proximal longitudinal retraction of the second part relative to thefirst part, the first part collapses from the expanded state to thecollapsed state.

A distal end of each of the first plurality of splines may be coupled toone spline of the second plurality of splines.

The distal end of each of the first plurality of splines may be coupledto one spline of the second plurality of splines proximal to a distalend of the one of the second plurality of splines. The distal ends ofthe second plurality of splines may comprise fixation elements. At leastsome of the first plurality of splines may comprise electrodes. Eachspline of the first plurality of splines may comprise a plurality ofelectrodes. The plurality of electrodes may at least partially formingan electrode matrix.

The device may further comprise a membrane coupled to the firstplurality of splines, the membrane comprising a plurality of electrodes,the plurality of electrodes at least partially forming an electrodematrix. A longitudinal length from a proximal end of a proximal-mostelectrode of the plurality of electrodes to a distal end of adistal-most electrode the plurality of electrodes may be between 20 mmand 40 mm. A diameter of the first plurality of splines in the expandedstate may be between 15 mm and 35 mm.

The device may further comprise a catheter coupled to the first annularportion and an inner member in a lumen of the catheter and coupled tothe second annular portion. The inner member may be movable relative tothe catheter to distally advance and proximally retract the second part.A proximal end of the first annular portion may be coupled in a distalend of a lumen of the catheter. A proximal end of the second annularportion may be coupled in a distal end of a lumen of the inner member.The inner member may be trackable over a guidewire.

The device may further comprise a gripper coupled to the inner member, aspring engaging the gripper, and a handle element coupled to the innermember. Upon distal advancement of the handle element, the spring may belongitudinally expanded, the inner member may be distally longitudinallyadvanced, the second part may be distally longitudinally advanced, andthe first part may expand from the collapsed state to the expandedstate. Upon proximal retraction of the handle element, the spring may belongitudinally compressed, the inner member may be proximallylongitudinally retracted, the second part may be proximallylongitudinally retracted, and the first part collapses from the expandedstate to the collapsed state. The spring may be configured to at leastpartially proximally retract the handle element.

The device may further comprise a locking mechanism configured tomaintain the handle element in a distally advanced state. The lockingelement may comprise a plurality of arms having an open proximal end.The handle element may be configured to extend through the open proximalend upon distal advancement. The locking element may comprise aplurality of arms having closed proximal end. The handle element may beconfigured to engage the closed proximal end upon distal advancement.The plurality of arms may comprise leaf springs. The leaf springs may beconfigured to at least partially proximally retract the handle element.

The first plurality of splines may be not self-expanding. The firstplurality of splines may be self-expanding. The first plurality ofsplines may comprise a non-tapered shape in the expanded state. Thefirst part may comprise a first cut hypotube. The first annular portionmay comprise a hypotube and the first plurality of splines may comprisea plurality of wires. The second part may comprise second a cuthypotube.

In some embodiments, a device comprises or consists essentially of aplurality of splines, a structure coupled to at least one spline of theplurality of splines, and an electrode coupled to the structure.

The device may comprise a plurality of electrodes coupled to thestructure. The plurality of electrodes may be the electrode. Theplurality of electrodes may at least partially form an electrode matrix.The electrode matrix may comprise a 3×4 matrix.

The structure may be coupled to at least two splines of the plurality ofsplines. The electrode may be circumferentially between two splines ofthe plurality of splines. The electrode may be circumferentially alignedwith a spline of the plurality of splines.

The device may further comprise a second electrode coupled to one of theplurality of splines. The structure may comprise a plurality of flexiblestrands connected to form a pattern of openings. The structure maycomprise a mesh. The structure may comprise a woven or knitted membrane.The structure may comprise shape memory material having an expandedshape when not confined. The structure may comprise insulative material.

In some embodiments, a device comprises or consists essentially of afirst sidewall, a second sidewall spaced from the first sidewall, and athird sidewall between the first sidewall and the second sidewall. Thefirst sidewall, the second sidewall, and the third sidewall at leastpartially define a U-shaped trough. The device further comprises aplurality of conductors in the trough and an electrode electricallyconnected to one of the plurality of conductors.

The device may comprise a plurality of electrodes including theelectrode. The plurality of electrodes may at least partially form anelectrode matrix. Each of the plurality of electrodes may beelectrically connected to one of the plurality of conductors. Theelectrode may have a dome shape.

The device may further comprise insulative material between theplurality of conductors and the electrode. The device may furthercomprise insulative material between the plurality of conductors and thethird sidewall. The device may further comprise insulating materialextending at least above a bottom of the electrode. The insulatingmaterial may comprise a dome shape. The insulating material may comprisea flat upper surface. The insulating material may comprise a crownedsurface. The insulating material may cover a sharp edge of theelectrode.

The electrode may have no uninsulated sharp edges. The electrode may beconfigured to be spaced from a vessel wall surface.

In some embodiments, a system comprises a plurality of the devices. Theplurality of devices may at least partially form an electrode matrix.

In some embodiments, a device comprises or consists essentially of acatheter comprising a lumen, a fixation structure, and a fixationelement. The fixation structure comprises a first side, a second side,and a twist. The fixation element is coupled to the first side of thefixation structure. The first side faces radially inwardly when thefixation structure is inside the lumen of the catheter and facesradially outwardly when the fixation structure is outside the lumen ofthe catheter.

The lumen may be shaped to correspond to a shape of the fixationstructure and the fixation element. The twist may be 180°. The fixationstructure may comprise a ribbon. The fixation structure may comprise astrut. The fixation structure may be configured to bend radially outwardupon deployment from the catheter. The fixation element may comprise aconical spike.

In some embodiments, a device may comprise or consists essentially of afixation structure, a fixation mechanism, and an attachment pointcoupling the fixation structure to the fixation mechanism. The fixationmechanism is configured to turn radially outward upon expansion of thefixation structure. The fixation mechanism is configured to turnradially inward upon collapse of the fixation structure. In an expandedstate, the fixation mechanism extends radially outward of the fixationstructure.

The fixation mechanism may comprise an aperture. The device may furthercomprise a radiopaque marker coupled to the fixation mechanism.

The device may further comprise a tether extending proximally from theattachment point. Tether may comprise a bend along a longitudinal lengthof the fixation mechanism. The bend may be between 30% and 70% of thelongitudinal length of the fixation mechanism. The tether may comprise aramped portion having a wide edge coupled to the attachment point. Thetether may comprise a twist proximal to the attachment point.

The device may further comprise a second fixation mechanism extendingdistally from the fixation structure. The fixation structure, thefixation element, and the attachment point may be monolithically cutfrom a same hypotube. The fixation structure may comprise an electrode.The fixation structure may comprise a plurality of electrodes includingthe electrode. The plurality of electrodes may at least partially forman electrode matrix.

In some embodiments, a method of forming a device comprises or consistsessentially of cutting a hypotube to form a fixation structure, afixation mechanism, and an attachment point coupling the fixationstructure and the fixation mechanism, and shape setting an expandedshape. The expanded shape includes the fixation mechanism bent radiallyoutward of the fixation structure. After shape setting the expandedshape, the fixation mechanism is configured to turn radially outwardupon expansion of the fixation structure and the fixation mechanism isconfigured to turn radially inward upon collapse of the fixationstructure.

Cutting the hypotube may comprise laser cutting the hypotube. Cuttingthe hypotube may comprise forming a tether extending proximally from theattachment point. Shape setting may comprise bending the tether along alongitudinal length of the fixation mechanism. Bending the tether may bebetween 30% and 70% of the longitudinal length of the fixationmechanism. Shape setting may comprise bending the tether at a proximalend of the attachment point. Shape setting may comprise forming a twistin the tether proximal to the attachment point.

In some embodiments, a device comprises or consists essentially of afixation structure, a fixation arm, and a fixation mechanism coupled tothe fixation arm. The fixation structure comprises an aperture, a firstsurface, and a second surface opposite the first surface. The fixationarm is coupled to an inside of the aperture of the fixation structure.The fixation arm does not protrude above the first surface in a firststate.

The fixation arm may be configured to flex radially outward when notconfined by a catheter. The fixation mechanism may protrude above thefirst surface when the fixation arm is not confined by the catheter. Thefixation arm may be configured to remain stationary when not confined bya catheter. The fixation mechanism may not protrude above the firstsurface when the fixation arm may be not confined by the catheter.

The fixation structure and the fixation arm may be formed from a samepiece of material. The aperture may extend from the first surface to thesecond surface. The aperture may extends from the first surface to apoint above the second surface. The fixation mechanism may comprise aconical spike. The fixation mechanism may comprise a textured surface.

In some embodiments, a device comprises or consists essentially of acatheter comprising a lumen, a first loop longitudinally movable from inthe lumen of the catheter to out of the lumen of the catheter, and asecond loop longitudinally movable from in the lumen of the catheter toout of the lumen of the catheter. At least one of the catheter, thefirst loop, and the second loop comprises a first electrode. At leastone of the first loop and the second loop may be a pigtail at an end ofa finger.

The first loop may comprise a first plurality of electrodes includingthe first electrode. The first plurality of electrodes may at leastpartially form a first electrode matrix. The second loop may comprise asecond plurality of electrodes. The second plurality of electrodes mayat least partially form a second electrode matrix. The second loop maycomprise a second electrode.

The first loop may comprise a first portion comprising electrodes of thefirst plurality of electrodes and a second portion comprising electrodesof the first plurality of electrodes. The second portion may be spacedfrom the first portion. The second portion may be parallel to the firstportion.

The first loop may comprise an undulating segment comprising peaks andtroughs. The undulating segment may comprise the first plurality ofelectrodes. The undulating segment may comprise electrodes of the firstplurality of electrodes proximate to the peaks and electrodes of thefirst plurality of electrodes proximate to the troughs.

The catheter may comprise a plurality of electrodes including the firstelectrode. The first plurality of electrodes may at least partially forma first electrode matrix.

The first loop and the second loop may be configured to be deployed fromthe lumen of the catheter at least partially simultaneously. The firstloop and the second loop may be configured to be deployed from the lumenof the catheter sequentially.

The device may further comprise a fixation feature extending radiallyoutward from the catheter. The fixation feature may comprise anatraumatic stiff loop.

In some embodiments, a method of using the device may comprise orconsist essentially of advancing the catheter distal to a pulmonaryvalve, advancing the catheter distal to the pulmonary valve, deployingthe first loop and the second loop, and after deploying the first loopand the second loop, distally advancing the catheter towards a pulmonaryartery bifurcation. The first loop and the second loop areself-orienting so that one of the first loop and the second loop extendsinto the right pulmonary artery and the other of the first loop and thesecond loop extends into the left pulmonary artery.

The method may further comprise distally advancing the catheter untiladvancement may be limited by the pulmonary artery bifurcation. Themethod may further comprise extending a fixation feature proximate tothe pulmonary valve. The method may further comprise attempting tocapture a target nerve with the first electrode.

The method may further comprise, if the target nerve may be notcaptured, withdrawing the first loop and the second loop into the lumenof the catheter, proximally retracting the catheter, rotating thecatheter, after rotating the catheter, redeploying the first loop andthe second loop, and, after redeploying the first loop and the secondloop, distally advancing the catheter towards the pulmonary arterybifurcation. The first loop and the second loop are self-orienting sothat one of the first loop and the second loop extends into the rightpulmonary artery and the other of the first loop and the second loopextends into the left pulmonary artery in an opposite orientation. Themethod may further comprise, if the target nerve may be not captured,attempting to capture a target nerve with a second electrode.

In some embodiments, a device comprises, or alternatively consistsessentially of, a catheter comprising a lumen and a loop longitudinallymovable from in the lumen of the catheter to out of the lumen of thecatheter. At least one of the catheter and the loop comprises a firstelectrode.

The loop may comprise a first plurality of electrodes including thefirst electrode. The first plurality of electrodes may at leastpartially form a first electrode matrix.

The loop may comprise a first portion comprising electrodes of the firstplurality of electrodes and a second portion comprising electrodes ofthe first plurality of electrodes. The second portion may be spaced fromthe first portion. The second portion may be parallel to the firstportion.

The loop may comprise an undulating segment comprising peaks andtroughs. The undulating segment may comprise the first plurality ofelectrodes. The undulating segment may comprise electrodes of the firstplurality of electrodes proximate to the peaks and electrodes of thefirst plurality of electrodes proximate to the troughs.

The catheter may comprise a first plurality of electrodes including thefirst electrode. The first plurality of electrodes may at leastpartially form a first electrode matrix.

The loop may be configured to be deployed from the lumen of the catheterout of a distal end of the catheter. The loop may be configured to bedeployed from the lumen of the catheter out of a side of the catheter.

The device may further comprise a fixation feature extending radiallyoutward from the catheter. The fixation feature may comprise anatraumatic stiff loop.

The loop may be a pigtail at an end of a finger.

A method of using the device may comprise deploying the loop out of thelumen of the catheter; after deploying the loop, advancing the catheterin a first branch vessel towards a primary vessel; allowing the loop toradially expand at a bifurcation comprising the first branch vessel, theprimary vessel, and a second branch vessel; and after allowing the loopto radially expand, proximally retracting the catheter until the loopcontacts the second branch vessel.

The first branch vessel may comprise the left internal jugular vein, theprimary vessel may comprise the left brachiocephalic vein, and thesecond branch vessel may comprise the left subclavian vein.

The method may further comprise extending a fixation feature.

The method may further comprise attempting to capture a target nervewith the first electrode. The target nerve may comprise a thoraciccardiac branch nerve. The target nerve may comprise a cervical cardiacnerve.

The catheter may comprise a curvature configured to bend towards thetarget nerve.

In some embodiments, a device comprises or consists essentially of acatheter comprising a lumen, a first sinusoidal wire, a secondsinusoidal wire radially spaced from the first sinusoidal wire, and aplurality of electrodes.

Each of the plurality of electrodes may be coupled to at least one thefirst sinusoidal wire and the second sinusoidal wire.

The device may further comprise a membrane coupled to the firstsinusoidal wire and the second sinusoidal wire. Each of the plurality ofelectrodes may be coupled to the membrane. The membrane may beconfigured to have a curved shape in an expanded state. The membrane maycomprise a flex circuit including conductor wires.

The plurality of electrodes may comprise button electrodes. Theplurality of electrodes may comprise barrel electrodes. The plurality ofelectrodes may comprise cylindrical electrodes. The plurality ofelectrodes may comprise directional electrodes. Centers the plurality ofelectrodes may be longitudinally offset.

The catheter may comprise a first segment and a second segment distal tothe first segment. The first segment may have a circular cross-section.The second segment may have an oval cross-section. The second segmentmay be configured to contain the first sinusoidal wire and the secondsinusoidal wire.

The first sinusoidal wire and the second sinusoidal wire may be planarin an expanded state. The first sinusoidal wire and the secondsinusoidal wire may be at an angle in an expanded state. The firstsinusoidal wire and the second sinusoidal wire may comprise shape memorymaterial.

In some embodiments, a device comprises, or alternatively consistsessentially of, a handle, a sheath, and an electrode system moveable inand out of the sheath. The handle comprises a repositioning system. Therepositioning system comprises a track and a knob slideable within thetrack. The electrode system is configured to move longitudinally uponlongitudinal movement of the knob in the track and to move rotationallyupon transverse or rotational movement of the knob in the track.

The track may comprise a longitudinal segment, a first transversesegment extending from the longitudinal segment in a first direction,and a second transverse segment extending from the longitudinal segmentin a second direction opposite the first direction. The first transversesegment may be longitudinally offset from the second transverse segment.The first transverse segment may be longitudinally aligned with thesecond transverse segment.

The electrode system may be configured to move a longitudinal distanceupon movement of the knob the same longitudinal distance in the track.The electrode system may be configured to rotate a circumferential angleupon transverse or rotational movement of the knob in the track. Thedevice may further comprise a rotational stop to limit rotation of theelectrode system to the circumferential angle.

The device may further comprise a detent and a groove configured tointeract with the detent upon movement of the knob. The detent may beconfigured to produce audible indicia.

The device may further comprise a physical barrier configured to inhibitaccidental movement of the knob.

In some embodiments, a device comprises, or alternatively consistsessentially of, an expandable structure having a collapsed state and anexpanded state. The expandable structure comprises, in the expandedstate, a plurality of splines each comprising a proximal segmentcomprising a first portion, a second portion distal to the firstportion, and a third portion distal to the second portion; anintermediate segment distal to the proximal segment; and a distalsegment distal to the intermediate segment, the distal segmentcomprising a fourth portion, a fifth portion distal to the fourthportion, and a sixth portion distal to the fifth portion. The firstportion is parallel to a longitudinal axis. The second portion extendsradially outward from the first portion. The third portion extendsradially outward from the second portion and transverse to thelongitudinal axis to the intermediate segment. The fourth portionextends from the intermediate segment radially inward and transverse tothe longitudinal axis. The fifth portion extends radially inward fromthe fourth portion. The sixth portion extends from the fifth portionparallel to a longitudinal axis. At least two of the intermediatesegments of the plurality of splines are circumferentially spaced andcomprise a plurality of electrodes forming an electrode matrix.

The expandable structure may be self-expanding. The expandable structuremay be expandable upon operation of an actuation mechanism.

In the expanded state, the at least two intermediate segments may beparallel to the longitudinal axis. In the expanded state, the at leasttwo intermediate segments may be recessed relative to the longitudinalaxis. In the expanded state, the at least two intermediate segments maybe crowned relative to the longitudinal axis.

Pairs of the first portions of the plurality of splines may be parallel.Pairs of the sixth portions of the plurality of splines may be parallel.Pairs of the first portions of the plurality of splines may be twisted.Pairs of the sixth portions of the plurality of splines may be twisted.

Proximal ends of the intermediate segments of the plurality of splinesmay be longitudinally aligned. Proximal ends of the intermediatesegments of the plurality of splines may be longitudinally offset.Distal ends of the intermediate segments of the plurality of splines maybe longitudinally aligned. Distal ends of the intermediate segments ofthe plurality of splines may be longitudinally offset.

The plurality of splines may further comprise a spline circumferentiallybetween the at least two intermediate segments.

The plurality of splines may comprise a plurality of wires. Theplurality of splines may be formed from a cut hypotube.

The expandable structure may further comprise a membrane coupled to theat least two intermediate segments. The membrane may comprise theelectrode matrix.

The device may further comprise a proximal portion and a catheter shaftcoupled to the proximal portion and coupled to the expandable structure.The device may further comprise an actuator wire. The proximal portionmay comprise an actuator mechanism. The actuator wire may be coupled tothe actuator mechanism and coupled to the expandable structure. Theexpandable structure may be configured to expand upon operation of theactuator mechanism. The proximal portion may comprise a Y-connectorcomprising a first branch configured to accept a guidewire and a secondbranch configured to electrically connect the electrode matrix to astimulation system.

The device may further comprise a strain relief between the cathetershaft and the expandable structure. The strain relief may comprise aspring. The strain relief may comprise a cut hypotube. The cut hypotubemay comprise a plurality of helices having the same sense.

The expandable structure may comprise a distal hub comprising aplurality of channels. The distal segments of the plurality of splinesmay be slideable in the channels of the distal hub. The distal segmentsmay comprise a distal end having a dimension larger than a dimension ofthe channels.

In some embodiments, a device comprises, or alternatively consistsessentially of, an expandable structure having a collapsed state and anexpanded state. The expandable structure comprises, in the expandedstate, a plurality of arms each comprising a proximal segment, anintermediate segment distal to the proximal segment, and a distalsegment distal to the intermediate segment. The intermediate segments ofthe plurality of arms include an opening. At least two the intermediatesegments of the plurality of splines comprise a plurality of electrodesforming an electrode matrix.

The expandable structure may be self-expanding. The expandable structuremay be expandable upon operation of an actuation mechanism.

In the expanded state, the at least two intermediate segments may beparallel to the longitudinal axis. In the expanded state, the at leasttwo intermediate segments may be recessed relative to the longitudinalaxis. In the expanded state, the at least two intermediate segments maybe crowned relative to the longitudinal axis.

Pairs of the first portions of the plurality of splines may be parallel.Pairs of the sixth portions of the plurality of splines may be parallel.Pairs of the first portions of the plurality of splines may be twisted.Pairs of the sixth portions of the plurality of splines may be twisted.

Proximal ends of the intermediate segments of the plurality of splinesmay be longitudinally aligned. Proximal ends of the intermediatesegments of the plurality of splines may be longitudinally offset.Distal ends of the intermediate segments of the plurality of splines maybe longitudinally aligned. Distal ends of the intermediate segments ofthe plurality of splines may be longitudinally offset.

The plurality of splines may further comprise a spline circumferentiallybetween the at least two intermediate segments.

The plurality of splines may comprise a plurality of wires. Theplurality of splines may be formed from a cut hypotube.

The expandable structure may further comprise a membrane coupled to theat least two intermediate segments. The membrane may comprise theelectrode matrix.

The device may further comprise a proximal portion and a catheter shaftcoupled to the proximal portion and coupled to the expandable structure.The device may further comprise an actuator wire. The proximal portionmay comprise an actuator mechanism. The actuator wire may be coupled tothe actuator mechanism and coupled to the expandable structure. Theexpandable structure may be configured to expand upon operation of theactuator mechanism. The proximal portion may comprise a Y-connectorcomprising a first branch configured to accept a guidewire and a secondbranch configured to electrically connect the electrode matrix to astimulation system.

The device may further comprise a strain relief between the cathetershaft and the expandable structure. The strain relief may comprise aspring. The strain relief may comprise a cut hypotube. The cut hypotubemay comprise a plurality of helices having the same sense.

The expandable structure may comprise a distal hub comprising aplurality of channels. The distal segments of the plurality of splinesmay be slideable in the channels of the distal hub. The distal segmentsmay comprise a distal end having a dimension larger than a dimension ofthe channels.

In some embodiments, a device comprises, or alternatively consistsessentially of, an expandable structure having a collapsed state and anexpanded state. The expandable structure comprises, in the expandedstate, a plurality of splines each comprising a proximal segmentcomprising a first portion, a second portion distal to the firstportion, and a third portion distal to the second portion; anintermediate segment distal to the proximal segment; and a distalsegment distal to the intermediate segment, the distal segmentcomprising a fourth portion, a fifth portion distal to the fourthportion, and a sixth portion distal to the fifth portion. The firstportion is parallel to a longitudinal axis. The second portion extendsradially outward from the first portion. The third portion extendsradially outward from the second portion and transverse to thelongitudinal axis to the intermediate segment. The fourth portionextends from the intermediate segment radially inward and transverse tothe longitudinal axis. The fifth portion extends radially inward fromthe fourth portion. The sixth portion extends from the fifth portionparallel to a longitudinal axis. The intermediate segments of theplurality of splines have an undulating shape relative to thelongitudinal axis. At least two of the intermediate segments of theplurality of splines comprise a plurality of electrodes forming anelectrode matrix.

The expandable structure may be self-expanding. The expandable structuremay be expandable upon operation of an actuation mechanism.

Pairs of the first portions of the plurality of splines may be parallel.Pairs of the sixth portions of the plurality of splines may be parallel.Pairs of the first portions of the plurality of splines may be twisted.Pairs of the sixth portions of the plurality of splines may be twisted.

Proximal ends of the intermediate segments of the plurality of splinesmay be longitudinally aligned. Proximal ends of the intermediatesegments of the plurality of splines may be longitudinally offset.Distal ends of the intermediate segments of the plurality of splines maybe longitudinally aligned. Distal ends of the intermediate segments ofthe plurality of splines may be longitudinally offset.

The intermediate segments may comprise peaks and troughs. Peaks andtroughs of the at least two intermediate segments may be longitudinallyaligned. Peaks and troughs of the at least two intermediate segments maybe longitudinally offset.

The plurality of splines may comprise a plurality of wires. Theplurality of splines may be formed from a cut hypotube.

The expandable structure may further comprise a membrane coupled to theat least two intermediate segments. The membrane may comprise theelectrode matrix.

The device may further comprise a proximal portion and a catheter shaftcoupled to the proximal portion and coupled to the expandable structure.The device may further comprise an actuator wire. The proximal portionmay comprise an actuator mechanism. The actuator wire may be coupled tothe actuator mechanism and coupled to the expandable structure. Theexpandable structure may be configured to expand upon operation of theactuator mechanism. The proximal portion may comprise a Y-connectorcomprising a first branch configured to accept a guidewire and a secondbranch configured to electrically connect the electrode matrix to astimulation system.

The device may further comprise a strain relief between the cathetershaft and the expandable structure. The strain relief may comprise aspring. The strain relief may comprise a cut hypotube. The cut hypotubemay comprise a plurality of helices having the same sense.

The expandable structure may comprise a distal hub comprising aplurality of channels. The distal segments of the plurality of splinesmay be slideable in the channels of the distal hub. The distal segmentsmay comprise a distal end having a dimension larger than a dimension ofthe channels.

In some embodiments, a device comprises, or alternatively consistsessentially of, an expandable structure having a collapsed state and anexpanded state. The expandable structure comprises, in the expandedstate, a plurality of arms each comprising a proximal segment, anintermediate segment distal to the proximal segment, and a distalsegment distal to the intermediate segment. The intermediate segments ofthe plurality of arms include a sinusoidal shape. At least two theintermediate segments of the plurality of splines comprise a pluralityof electrodes forming an electrode matrix.

The expandable structure may be self-expanding. The expandable structuremay be expandable upon operation of an actuation mechanism.

Pairs of the first portions of the plurality of splines may be parallel.Pairs of the sixth portions of the plurality of splines may be parallel.Pairs of the first portions of the plurality of splines may be twisted.Pairs of the sixth portions of the plurality of splines may be twisted.

Proximal ends of the intermediate segments of the plurality of splinesmay be longitudinally aligned. Proximal ends of the intermediatesegments of the plurality of splines may be longitudinally offset.Distal ends of the intermediate segments of the plurality of splines maybe longitudinally aligned. Distal ends of the intermediate segments ofthe plurality of splines may be longitudinally offset.

The intermediate segments may comprise peaks and troughs. Peaks andtroughs of the at least two intermediate segments may be longitudinallyaligned. Peaks and troughs of the at least two intermediate segments maybe longitudinally offset.

The plurality of splines may comprise a plurality of wires. Theplurality of splines may be formed from a cut hypotube.

The expandable structure may further comprise a membrane coupled to theat least two intermediate segments. The membrane may comprise theelectrode matrix.

The device may further comprise a proximal portion and a catheter shaftcoupled to the proximal portion and coupled to the expandable structure.The device may further comprise an actuator wire. The proximal portionmay comprise an actuator mechanism. The actuator wire may be coupled tothe actuator mechanism and coupled to the expandable structure. Theexpandable structure may be configured to expand upon operation of theactuator mechanism. The proximal portion may comprise a Y-connectorcomprising a first branch configured to accept a guidewire and a secondbranch configured to electrically connect the electrode matrix to astimulation system.

The device may further comprise a strain relief between the cathetershaft and the expandable structure. The strain relief may comprise aspring. The strain relief may comprise a cut hypotube. The cut hypotubemay comprise a plurality of helices having the same sense.

The expandable structure may comprise a distal hub comprising aplurality of channels. The distal segments of the plurality of splinesmay be slideable in the channels of the distal hub. The distal segmentsmay comprise a distal end having a dimension larger than a dimension ofthe channels.

In some embodiments, a device comprises, or alternatively consistsessentially of, a longitudinal axis and a distal portion. The distalportion comprises a first expandable structure and a second expandablestructure distal to the first expandable structure. The first expandablestructure has a collapsed state and an expanded state. The expandablestructure comprises, in the expanded state, a plurality of arms eachcomprising a proximal segment, an intermediate segment distal to theproximal segment, and a distal segment distal to the intermediatesegment. The plurality of arms is on a first side of a plane comprisingthe longitudinal axis. At least two the intermediate segments of theplurality of splines comprise a plurality of electrodes forming anelectrode matrix; and

The second expandable structure may comprise a Swan-Ganz balloon. Thesecond expandable structure may be distal to the first expandablestructure by between 0.25 cm and 5 cm.

The first expandable structure may be self-expanding. The firstexpandable structure may be expandable upon operation of an actuationmechanism.

The plurality of splines may comprise a plurality of wires. Theplurality of splines may be formed from a cut hypotube.

The first expandable structure may further comprise a membrane coupledto the at least two intermediate segments. The membrane may comprise theelectrode matrix.

The device may further comprise a proximal portion and a catheter shaftcoupled to the proximal portion and coupled to the expandable structure.The catheter shaft may be configured to appose a wall of a body cavity.The device may further comprise an actuator wire. The proximal portionmay comprise an actuator mechanism. The actuator wire may be coupled tothe actuator mechanism and coupled to the first expandable structure.The first expandable structure may be configured to expand uponoperation of the actuator mechanism. The proximal portion may comprise aY-connector comprising a first branch configured to accept a guidewireand a second branch configured to electrically connect the electrodematrix to a stimulation system.

The first expandable structure may comprise a distal hub comprising aplurality of channels. Distal segments of the plurality of splines maybe slideable in the channels of the distal hub. The distal segments maycomprise a distal end having a dimension larger than a dimension of thechannels.

The device may further comprise a tubular member extending from theproximal portion to the second expandable structure. The tubular membermay comprise a lumen configured to inflate the second expandablestructure upon injection of fluid into the lumen. The tubular member maybe coupled to the distal segments of the plurality of arms. The firstexpandable structure may expand upon proximal retraction of the tubularmember.

In some embodiments, a method of processing an electrocardiogram signalcomprising P waves and S waves comprises, or alternatively consistessentially of, detecting an end of a first S wave, estimating a startof a first P wave, and during a stimulation duration between detectingthe end of the first S wave and the estimated start of the first P wave,providing an artificial signal. A non-transitory computer-readablemedium may store executable instructions that when executed perform themethod.

The artificial signal may comprise a straight line. The straight linemay be at a negative value. The straight line may be at a positivevalue.

In some embodiments, an electrocardiogram signal comprises, oralternatively consist essentially of, a first portion indicative of anelectrical activity of a heart during a first duration and a secondportion not indicative of the electrical activity of the heart during asecond duration after the first duration. The first duration is lessthan a sinus rhythm. A non-transitory computer-readable medium may beconfigured to store the signal.

The first portion may comprise a QRS complex. The first portion maycomprise a PR interval. The second portion may comprise a ST segment.The second portion may comprise a straight line. The straight line maybe at a negative value. The straight line may be at a positive value.

In some embodiments, a method of processing an electrocardiogram signalcomprises, or alternatively consist essentially of, detecting a firstcondition of a first type of wave selected from the group consisting ofP waves, Q waves, R waves, S waves, and T waves; after a stimulationduration starting after detecting the first condition of the first typeof wave, monitoring for a monitoring duration for second condition of asecond type of wave selected from the group consisting of P waves, Qwaves, R waves, S waves, and T waves, the second type of wave differentthan the first type of wave; and if the second condition of the secondtype of wave may be not detected during the monitoring duration,triggering a physical event. A non-transitory computer-readable mediummay store executable instructions that when executed perform the method.

The first condition may comprise a beginning of the first type of wave.The first condition may comprise an end of the first type of wave. Thefirst condition may comprise a peak of the first type of wave. Thesecond condition may comprise a beginning of the second type of wave.The second condition may comprise an end of the second type of wave. Thesecond condition may comprise a peak of the second type of wave. Thesecond condition may comprise a peak of the second type of wave. Thefirst type of wave may comprise a S wave. The second type of wave maycomprise a P wave. The second type of wave may comprise a Q wave. Thesecond type of wave may comprise a R wave. The physical event maycomprise terminating stimulation. The physical event may comprisesounding an alarm.

In some embodiments, a method of processing an electrocardiogram signalcomprises, or alternatively consist essentially of, providing a firstportion indicative of electrical activity of a heart during a firstduration, the first portion comprising a real P wave, a real Q wave, areal R wave, a real S wave, and a real T wave; and providing a secondportion not indicative of the electrical activity of the heart during asecond duration after the first duration, stimulation of the heartoccurring during the second duration. A non-transitory computer-readablemedium may store executable instructions that when executed perform themethod.

The portion may comprise a straight line. The straight line may be atzero. The straight line may be at a negative value. The straight linemay be at a positive value.

The second portion may comprise a duplication of the first portion.

The second portion may comprise at least a portion of an artificialsinus rhythm. The portion of the artificial sinus rhythm may comprise atleast one of an artificial P wave, an artificial Q wave, an artificial Rwave, an artificial S wave, and an artificial T wave. The at least oneof an artificial P wave, an artificial Q wave, an artificial R wave, anartificial S wave, and an artificial T wave may be shaped like a realwave. The at least one of an artificial P wave, an artificial Q wave, anartificial R wave, an artificial S wave, and an artificial T wave may beshaped like a square wave.

In some embodiments, an electrocardiogram signal comprises, oralternatively consist essentially of, a first portion indicative ofelectrical activity of a heart during a first duration and a secondportion not indicative of the electrical activity of the heart during asecond duration after the first duration. The first portion comprises areal P wave, a real Q wave, a real R wave, a real S wave, and a real Twave. Stimulation of the heart occurs during the second duration. Anon-transitory computer-readable medium may be configured to store thesignal.

The second portion may comprise a straight line. The straight line maybe at zero. The straight line may be at a negative value. The straightline may be at a positive value.

The second portion may comprise a duplication of the first portion.

The second portion may comprise at least a portion of an artificialsinus rhythm.

The portion of the artificial sinus rhythm may comprise at least one ofan artificial P wave, an artificial Q wave, an artificial R wave, anartificial S wave, and an artificial T wave. The at least one of anartificial P wave, an artificial Q wave, an artificial R wave, anartificial S wave, and an artificial T wave may be shaped like a realwave. The at least one of an artificial P wave, an artificial Q wave, anartificial R wave, an artificial S wave, and an artificial T wave may beshaped like a square wave.

In some embodiments, a device comprises, or alternatively consistsessentially of, a handle, an expandable structure, an outer tube, and ashaft. The expandable structure has a collapsed state and aself-expanded state. The expandable structure comprises a plurality ofsplines extending from a proximal hub to a distal hub. Each of thesplines of the plurality of splines comprises a proximal segment, anintermediate segment distal to the proximal segment, a distal segmentdistal to the intermediate segment, and a first electrode on a firstspline of the plurality of splines. The intermediate segment isconfigured to extend radially outward in the self-expanded state. Theouter tube comprises a proximal end coupled to the handle and a distalend coupled to the proximal hub. The shaft comprises a proximal end anda distal end. The shaft extends through the outer tube from the handleto the distal hub. The handle is configured to retract the shaft. Theintermediate segments are configured to extend further radially outwardupon retraction of the shaft.

At least one spline of the plurality of splines may be devoid ofelectrodes. The intermediate segment of each spline of the plurality ofsplines may form a first angle with the proximal segment and/or a secondangle with the distal segment. The proximal segment and distal segmentof each spline of the plurality of splines may be devoid of electrodes.The first spline may comprise a first plurality of electrodes includingthe first electrode. The first plurality of electrodes may form anelectrode array. The device may further comprise a second electrode on asecond spline of the plurality of splines. The first spline may comprisea first plurality of electrodes including the first electrode. Thesecond spline may comprise a second plurality of electrodes includingthe second electrode. The first plurality of electrodes may comprisefive electrodes. The second plurality of electrodes may comprise fiveelectrodes. The first plurality of electrodes and the second pluralityof electrodes form an electrode array. The second spline may becircumferentially adjacent to the first spline. The first spline and thesecond spline may form a first spline pair. The device may furthercomprise a second spline pair. The second spline pair may comprise athird spline comprising a third plurality of electrodes and a fourthspline comprising a fourth plurality of electrodes. The fourth splinemay be circumferentially adjacent to the third spline. The second splinepair may be circumferentially adjacent to the first spline pair. Thefirst plurality of electrodes, the second plurality of electrodes, thethird plurality of electrodes, and the fourth plurality of electrodesmay form an electrode array. The electrode array may comprise a 4×5array. At least four circumferentially adjacent splines of the pluralityof splines may each comprise a plurality of electrodes. At least onespline of the plurality of splines may be devoid of electrodes. Theproximal segment and distal segment of each spline may be straight. Theintermediate segment of each spline may be concave. The proximal segmentand distal segment of each spline may be straight. The intermediatesegment of each spline may be convex. The proximal segment and distalsegment of each spline may be straight. The intermediate segment of eachspline may be straight. Each spline of the plurality of splines furthermay comprise a proximal transition segment joining the proximal segmentand the intermediate segment and a distal transition segment joining theintermediate segment and the distal segment. The splines may be groupedinto circumferentially adjacent spline pairs. Each spline of a splinemay be parallel to the other spline of the spline pair along theproximal segment, the intermediate segment, and the distal segment. Eachspline of the spline pair may be not parallel to the other spline of thespline pair along the proximal transition segment and the distaltransition segment. The intermediate segments of each spline pair may bespaced further apart from each other than the proximal segments and thedistal segments. The expandable structure may comprise a longitudinalaxis between the proximal hub and the distal hub. The proximal segmentsof each of the splines of the plurality of splines may radially divergeaway from the longitudinal axis and the distal segments of each of thesplines of the plurality of splines may radially converge towards thelongitudinal axis.

The outer tube may comprise a proximal portion and a distal portion. Theproximal portion may have a higher durometer than the distal portion.The outer tube may comprise a plurality of longitudinal portions along alength of the outer tube. Each longitudinal portion the plurality oflongitudinal portions may have a higher durometer than the longitudinalportions of the plurality of longitudinal portions distal thereto. Atleast one longitudinal portion of the plurality of longitudinal portionsmay be configured with a length and durometer for positioning the atleast one longitudinal portion in a specific anatomy. The specificanatomy may comprise a chamber of a heart. The specific anatomy maycomprise a blood vessel. The blood vessel may comprise the rightpulmonary artery. The outer tube may comprise a first outer diameter atthe proximal end of the outer tube and a second outer diameter at thedistal end of the outer tube. The first outer diameter may be greaterthan the second outer diameter. A proximal portion of the outer tube maycomprise a first plurality of layers, wherein a distal portion of theouter tube may comprise a second plurality of layers. The firstplurality of layers may comprise more layers than the second pluralityof layers. The outer tube may comprise a hinge joined to the proximalhub. The hinge may be configured to resist kinking upon bending of thedevice transverse to a longitudinal axis of the outer tube. The hingemay comprise a coil comprising a proximal end and a distal end, theproximal end of the coil surrounding a portion of the tubing and thedistal end of the coil surrounding a portion of the proximal hub. Thehinge may comprise a first wire comprising a helical winding, a secondwire comprising a helical winding and occupying spaces between helicesof the first wire, and a third wire comprising a helical winding andoccupying spaces between helices the first wire and between helices ofthe second wire. The outer tube may comprise tubing. The tubing maycomprise an inner diameter configured to mate with an outer diameter ofthe proximal hub. The tubing may be configured to abut a proximal end ofthe proximal hub. The tubing may form a fluid seal between the outertube and the proximal hub.

The spline comprising the electrode may comprise a spline tube, theelectrode being on an outer surface of the spline tube. The device mayfurther comprise a spline tube at least partially covering twocircumferentially adjacent splines of the plurality of splines. Thespline tube may be configured to inhibit the two circumferentiallyadjacent splines from rotating relative to one another. The spline tubemay diverge into two spatially separated tubular channels along theintermediate segments of the two circumferentially adjacent splines.Circumferentially adjacent splines of the plurality of splines may begrouped into spline pairs, each of the spline pairs comprising aproximal tubing at least partially covering the proximal segments and adistal tubing at least partially covering the distal segments. Theproximal tubings and the distal tubings may be configured to inhibit thesplines of each of the spline pairs from rotating relative to oneanother. Each of the proximal tubings and the distal tubings maycomprise heat-shrink tubing. Circumferentially adjacent splines of theplurality of splines may be grouped into spline pairs, each of thespline pairs comprising a wire bent at a proximal end, and may have wireends terminating at a distal end.

The proximal hub may comprise a proximal end, a distal end, a centrallumen, a plurality of peripheral lumens, and/or a plurality of splinechannels. The central lumen may extend from the proximal end of theproximal hub to the distal end of the proximal hub. The shaft mayslidably extend through the central lumen of the proximal hub. Theplurality of peripheral lumens may be radially outward of the centrallumen of the proximal hub. The plurality of peripheral lumens may beconfigured to transfer fluid flowing through the outer tube to thedistal end of the proximal hub. The plurality of spline channels mayextend proximally from the distal end of the proximal hub into a distalportion of the proximal hub. One spline of the plurality of splines maybe in each spline channel of the plurality of spline channels of theproximal hub. The plurality of spline channels may extend through thedistal portion of the proximal hub. Circumferentially adjacent splinesof the plurality of splines may be grouped into spline pairs, each ofthe spline pairs comprising a wire bent at a proximal end. The proximalhub may comprise a plurality of recesses proximal to the distal portionof the proximal hub. The bent proximal ends of the wire of each of thespline pairs may be in a recess of the plurality of recesses. Theplurality of recesses may be configured to inhibit movement of theplurality of splines proximal to the recesses. At least one peripherallumen of the plurality of peripheral lumens may be configured to receivean electrical conductor extending from the handle to the electrode.

The distal hub may comprise a proximal end, a distal end, a centrallumen, and/or a plurality of spline channels. The central lumen mayextend from the proximal end of the distal hub to the distal end of thedistal hub. The shaft may be fixably coupled to the central lumen of thedistal hub. A plurality of spline channels may extend distally from theproximal end of the distal hub into the distal hub. One spline of theplurality of splines may be in each spline channel of the plurality ofspline channels of the distal hub. Each spline channel of the pluralityof spline channels of the distal hub may terminate proximal to thedistal end of the distal hub. The proximal end of the distal hub maycomprise a tapered surface. The tapered surface of the proximal end ofthe distal hub may comprise openings to the plurality of splinechannels. The tapered surface proximal end of the distal hub may beconfigured to facilitate bending of the splines in a radially outwarddirection. The distal end of the distal hub may comprise an atraumaticconfiguration.

The handle may comprise a handle base and an actuator. The handle basemay comprise a proximal end, a distal end, and a lumen extending fromthe proximal end to the distal end. A proximal end of the outer tube maybe coupled to the lumen of the handle base, the shaft slidably extendingthrough the lumen of the handle base. An actuator may be affixed to aproximal end of the shaft, the actuator moveable relative to the handlebase in a proximal direction and in a distal direction. The actuator maybe configured to expand the expandable structure when moved in a distaldirection and to compress the expandable structure when moved in aproximal direction. The handle further may comprise an outer handle, asecuring member, and/or a locking member. The outer handle may extendfrom the handle base. The securing member may comprise a proximal endaffixed to the actuator. The locking member may be positioned along thesecuring member between the outer handle and the actuator. The lockingmember may be configured to be moved along the longitudinal axis of thesecuring member and secured at a position along a length of the securingmember to inhibit movement of the actuator in a distal direction. Thesecuring member may comprise a threaded shaft and the locking member maycomprise a threaded channel. The locking member may be longitudinallymoveable along the securing member by rotating the locking member aroundthe threaded shaft.

The handle may comprise a locking member having a locked configurationand an unlocked configuration. The locking member may comprise a mainbody comprising a proximal end and a distal end, a channel extendingfrom the proximal end to the distal end, and a protrusion extending intothe channel of the locking member. The actuator may extend through thechannel of the locking member. The protrusion may be configured toinhibit the actuator from moving in at least one of a proximal directionand a distal direction relative to the handle base when the lockingmember is in the locked configuration. The actuator may be moveable inthe proximal direction and in the distal direction when the lockingmember is in the unlocked configuration. The actuator may comprise anelongate body and a textured surface along a length of the elongatebody. The locking member may be moveable between the lockedconfiguration and the unlocked configuration by rotating the lockingmember around the elongate body of the actuator. The protrusion may beconfigured to interface with the textured surface in a locked positionand configured to not interface with the textured surface in theunlocked position. The locking member may further comprise a tabextending away from the main body, the tab being positionable in a firstposition relative to the handle base when the locking member is in alocked configuration and being positionable in a second position whenthe locking member is in an unlocked configuration. The textured surfacemay comprise a series of ridges, the protrusion of the locking memberconfigured to mate with a notch between the ridges. The channel of thelocking member may be oblong. The locking member may be configured toswitch between a locked configuration and an unlocked configuration byrotating the locking member approximately a quarter turn. The handlebase may further comprise an aperture in a sidewall extending into thelumen of the handle base and proximal to the proximal end of the outertube. An electrical conductor may extend from an electrical socket intothe outer tube through the aperture of the handle base.

The shaft may comprise a lumen. The lumen of the shaft may be configuredto receive a guidewire. A proximal end of the shaft may be configured toreceive fluid. The proximal end of the shaft may be joined to a fluidvalve. The shaft may comprise a sidewall and an aperture in thesidewall, the aperture configured to permit fluid to flow out of thelumen of the shaft and to the proximal hub. The device may be configuredto transfer fluid injected into the shaft through the shaft to thedistal hub and through the outer tube to the proximal hub. The shaft maycomprise a plurality of hypotubes. The plurality of hypotubes maycomprise a first hypotube having a proximal end and a distal end and asecond hypotube having a proximal end and a distal end. The distal endof the first hypotube may be in the proximal end of the second hypotube.The proximal end of the second hypotube may be in the distal end of thefirst hypotube. The plurality of hypotubes may include three hypotubes.At least one hypotube of the plurality of hypotubes may comprise aproximal portion having a first outer diameter and a distal portionhaving a second outer diameter less than the first outer diameter. Atleast one hypotube of the plurality of hypotubes may comprise a sidewalland an aperture through the sidewall.

In some embodiments, a method of modulating a nerve comprises, oralternatively consists essentially of, inserting a distal portion of adevice comprising an expandable structure into vasculature, allowing theexpandable member to self-expand, actuating a handle of the device tofurther expand the expandable structure to anchor the expandablestructure in the vasculature, and activating a first electrode of thedevice to stimulate the nerve. The device comprises a proximal portioncomprising the handle and the distal portion comprising the expandablestructure. The expandable structure has a collapsed state and aself-expanded state. The expandable structure comprises a plurality ofsplines extending from a proximal hub to a distal hub. Each of thesplines of the plurality of splines comprises a proximal segment, anintermediate segment distal to the proximal segment, and a distalsegment distal to the intermediate segment. The intermediate segment isconfigured to extend radially outward in the self-expanded state. Theexpandable structure comprises a first electrode on a first spline ofthe plurality of splines.

The device may comprise an outer tube and a shaft. The outer tube maycomprise a proximal end coupled to the handle and a distal end coupledto the proximal hub. The shaft may comprise a proximal end and a distalend and may extend through the outer tube from the handle to the distalhub. The handle may be configured to retract the shaft in a proximaldirection relative to the outer tube when the handle is actuated,causing the distal hub and the proximal hub to move closer together.

The method may further comprise accessing the vasculature with a needleand a syringe. The method may further comprise inserting a guidewireinto the vasculature. The shaft of the device may comprise a lumenextending from the proximal portion of the device to the distal portionof the device. The insertion of the distal portion of the device intothe vasculature may comprise inserting the device over the guidewiresuch that the guidewire may be slidably received in the lumen of theshaft. The method may further comprise tracking the guidewire to atarget location in the vasculature. The method may further compriseinserting a Swan-Ganz catheter into vasculature. The Swan-Ganz cathetermay comprise an inflatable balloon at a distal end of the catheter. Themethod may further comprise inflating the inflatable balloon, allowingthe balloon to be carried by blood flow to the target location,inserting the guidewire through a lumen in the Swan-Ganz catheter to thetarget location, deflating the inflatable balloon, and retracting theSwan-Ganz catheter from the vasculature. The target location may be theright pulmonary artery.

The method may further comprise inserting an introducer in thevasculature. The insertion of the distal portion of the medical deviceinto the vasculature may comprise inserting the device through a sheathof the introducer. The method may further comprise retracting a distalend of the introducer sheath from the distal portion of the deviceand/or pushing the distal portion of the device beyond the distal end ofthe sheath, causing the expandable structure to self-expand. The methodmay further comprise actuating a locking member on the handle to preventthe expandable structure from being compressed. The method may furthercomprise positioning the expandable structure in the right pulmonaryartery. The nerve may be a cardiopulmonary nerve. The expandablestructure may further comprise a second electrode on a second spline ofthe plurality of splines, the expandable structure being positioned suchthat the nerve may be positioned along the first spline, along thesecond spline, or between the first spline and the second spline. Themethod may further comprise activating the second electrode. The firstspline may be circumferentially adjacent the second spline. The firstspline may comprise a first plurality of electrodes including the firstelectrode, and the second spline may comprise a second plurality ofelectrodes including the second electrode. The first plurality ofelectrodes may comprise five electrodes and the second plurality ofelectrodes may comprise five electrodes. The first spline and the secondspline may form a first spline pair. The first plurality of electrodesand the second plurality of electrodes may form an electrode array. Theexpandable structure may further comprise a second spline paircomprising a third spline comprising a third plurality of electrodes anda fourth spline comprising a fourth plurality of electrodes. The firstplurality of electrodes, the second plurality of electrodes, the thirdplurality of electrodes, and the fourth plurality of electrodes may forman electrode array. The electrode array may comprise a 4×5 array. Themethod may further comprise positioning the expandable structure againsttissue in the vasculature so that the nerve may be between at least twoelectrodes apposed against the tissue. The nerve may be between at leastthree electrodes apposed against the tissue. The nerve may be between atleast four electrodes apposed against the tissue. Activating the firstelectrode may comprise applying a voltage pulse of a first polarity. Themethod may further comprise applying a pre-pulse of voltage to tissuesurrounding the nerve prior to activating the first electrode, thepre-pulse being a second polarity opposite the first polarity. Themethod may further comprise measuring the pressure in the rightventricle and approximating the pressure in the left ventricle from themeasured pressure in the right ventricle. The method may furthercomprise positioning a return conductor in the vasculature or on skin,the return conductor configured to conduct current from the activatedelectrode.

In some embodiments, a device for increasing heart contractility fortreating heart failure comprises, or alternatively consists essentiallyof, a handle, and an expandable structure. The expandable structure hasa collapsed state and a self-expanded state. The expandable structurecomprises a plurality of splines extending from a proximal hub to adistal hub. The device further comprises a first electrode on a firstspline of the plurality of splines, an outer tube extending from thehandle to the proximal hub, and a shaft extending through the outer tubefrom the handle to the distal hub. The handle is configured to retractthe shaft. The device is configured for placement in a pulmonary arteryand delivery of energy from the first electrode to a target tissue toincrease heart contractility for treating heart failure.

At least one spline of the plurality of splines may be devoid ofelectrodes.

The first spline may comprise a first plurality of electrodes includingthe first electrode. The first plurality of electrodes may form anelectrode array.

The device may further comprise a second electrode on a second spline ofthe plurality of splines. The first spline may comprise a firstplurality of electrodes including the first electrode. The second splinemay comprise a second plurality of electrodes including the secondelectrode. The first plurality of electrodes may comprise fiveelectrodes. The second plurality of electrodes may comprise fiveelectrodes. The first plurality of electrodes and the second pluralityof electrodes may form an electrode array. The second spline may becircumferentially adjacent to the first spline. The first spline and thesecond spline may form a first spline pair. The device may furthercomprise a second spline pair comprising a third spline comprising athird plurality of electrodes and a fourth spline comprising a fourthplurality of electrodes. The fourth spline may be circumferentiallyadjacent to the third spline. The second spline pair may becircumferentially adjacent to the first spline pair. The first pluralityof electrodes, the second plurality of electrodes, the third pluralityof electrodes, and the fourth plurality of electrodes form an electrodearray. The electrode array may comprise a 4×5 array. Each of at leastfour circumferentially adjacent splines of the plurality of splines maycomprise a plurality of electrodes.

Each of the splines of the plurality of splines may comprise a proximalsegment, an intermediate segment distal to the proximal segment, and adistal segment distal to the intermediate segment. The intermediatesegments may be configured to extend radially outward in theself-expanded state. The intermediate segments may be configured toextend further radially outward upon retraction of the shaft. Theintermediate segment of each spline of the plurality of splines may forma first angle with the proximal segment and a second angle with thedistal segment. The intermediate segment of each spline of the pluralityof splines may curve into the proximal segment and the distal segment.

The proximal segment and the distal segment of each spline of theplurality of splines may be devoid of electrodes.

The proximal segment and the distal segment of each spline may bestraight. The intermediate segment of each spline may be concave. Theintermediate segment of each spline may be convex. The intermediatesegment of each spline may be straight. Each of the proximal segment,the distal segment, and intermediate segment of each spline may bearcuate.

Each spline of the plurality of splines may further comprise a proximaltransition segment joining the proximal segment and the intermediatesegment, and a distal transition segment joining the intermediatesegment and the distal segment. Each spline of the spline pair may benot parallel to the other spline of the spline pair along the proximaltransition segment and the distal transition segment.

The first spline and a second spline of the plurality of splines mayform a first spline pair. The second spline may be circumferentiallyadjacent to the first spline. The device may further comprise a secondspline pair comprising a third spline of the plurality of splines and afourth spline to the plurality of splines. The fourth spline may becircumferentially adjacent to the third spline. Each spline of a splinepair may be parallel to the other spline of the spline pair along theintermediate segment. Each spline of a spline pair may be parallel tothe other spline of the spline pair along the proximal segment and thedistal segment. The intermediate segments of each spline pair may bespaced further apart from each other than the proximal segments and thedistal segments.

A least one spline of the plurality of splines may be devoid ofelectrodes.

The expandable structure may comprise a longitudinal axis between theproximal hub and the distal hub. The proximal segments of each of thesplines of the plurality of splines may radially diverge away from thelongitudinal axis and the distal segments of each of the splines of theplurality of splines may radially converge towards the longitudinalaxis.

The plurality of splines may be configured to extend outwardly on oneside of a plane crossing a longitudinal axis of the expandablestructure. Splines of the plurality of splines comprising electrodes maybe configured to extend outwardly on one side of a plane crossing alongitudinal axis of the expandable structure. The splines of theplurality of splines comprising electrodes may circumferentially occupy100° to 120°. Splines of the plurality of splines not comprisingelectrodes may be configured to extend outwardly on a second side of theplane crossing the longitudinal axis of the expandable structure. Thesecond side may be opposite the one side.

The outer tube may comprise a proximal portion and a distal portion. Theproximal portion may have a higher durometer than the distal portion.The outer tube may comprise a plurality of longitudinal portions along alength of the outer tube. Each longitudinal portion the plurality oflongitudinal portions may have a higher durometer than the longitudinalportions of the plurality of longitudinal portions distal thereto. Atleast one longitudinal portion of the plurality of longitudinal portionsmay be configured with a length and durometer for positioning the atleast one longitudinal portion in a specific anatomy. The specificanatomy may comprise a chamber of a heart. The specific anatomy maycomprise a blood vessel. The blood vessel may comprise the rightpulmonary artery.

The outer tube may comprise a first outer diameter at the proximal endof the outer tube and a second outer diameter at the distal end of theouter tube. The first outer diameter may be greater than the secondouter diameter.

A proximal portion of the outer tube may comprise a first plurality oflayers. A distal portion of the outer tube may comprise a secondplurality of layers. The first plurality of layers may comprise morelayers than the second plurality of layers.

The outer tube may comprise a hinge joined to the proximal hub. Thehinge may be configured to resist kinking upon bending of the devicetransverse to a longitudinal axis of the outer tube. The hinge maycomprise a coil comprising a proximal end and a distal end. The proximalend of the coil may surround a portion of the tubing and the distal endof the coil may surround a portion of the proximal hub. The hinge maycomprise a first wire comprising a helical winding, a second wirecomprising a helical winding and occupying spaces between helices of thefirst wire, and a third wire comprising a helical winding and occupyingspaces between helices the first wire and between helices of the secondwire.

The outer tube may comprise tubing. The tubing may comprise an innerdiameter configured to mate with an outer diameter of the proximal hub.The tubing may be configured to abut a proximal end of the proximal hub.The tubing may form a fluid seal between the outer tube and the proximalhub.

The first spline may comprise a spline tube. The first electrode may beon an outer surface of the spline tube.

The device may further comprise a spline tube at least partiallycovering two circumferentially adjacent splines of the plurality ofsplines. The spline tube may be configured to inhibit the twocircumferentially adjacent splines from rotating relative to oneanother. The spline tube may diverge into two spatially separatedtubular channels along the intermediate segments of the twocircumferentially adjacent splines.

Circumferentially adjacent splines of the plurality of splines may begrouped into spline pairs. Each of the spline pairs may comprise aproximal tubing at least partially covering the proximal segments and adistal tubing at least partially covering the distal segments. Theproximal tubings and the distal tubings may be configured to inhibit thesplines of each of the spline pairs from rotating relative to oneanother. Each of the proximal tubings and the distal tubings maycomprise heat-shrink tubing.

Circumferentially adjacent splines of the plurality of splines may begrouped into spline pairs. Each of the spline pairs may comprise a wirebent at a proximal end and having wire ends terminating at a distal end.

The proximal hub may comprise a proximal end, a distal end, and acentral lumen extending from the proximal end of the proximal hub to thedistal end of the proximal hub. The shaft may slidably extend throughthe central lumen of the proximal hub. The device may further comprise aplurality of peripheral lumens radially outward of the central lumen ofthe proximal hub. The plurality of peripheral lumens may be configuredto transfer fluid flowing through the outer tube to the distal end ofthe proximal hub. At least one peripheral lumen of the plurality ofperipheral lumens may be configured to receive an electrical conductorextending from the handle to the first electrode. The device may furthercomprise a plurality of spline channels extending proximally from thedistal end of the proximal hub into a distal portion of the proximalhub. One spline of the plurality of splines may be in each splinechannel of the plurality of spline channels of the proximal hub. Theplurality of spline channels may extend through the distal portion ofthe proximal hub. Circumferentially adjacent splines of the plurality ofsplines may be grouped into spline pairs. Each of the spline pairs maycomprise a wire bent at a proximal end. The proximal hub may comprise aplurality of recesses proximal to the distal portion of the proximalhub. The bent proximal ends of the wire of each of the spline pairs maybe in a recess of the plurality of recesses. The plurality of recessesmay be configured to inhibit movement of the plurality of splinesproximal to the recesses.

The distal hub may comprise a proximal end, a distal end, and a centrallumen extending from the proximal end of the distal hub to the distalend of the distal hub. The shaft may be fixably coupled to the centrallumen of the distal hub. The device may further comprise a plurality ofspline channels extending distally from the proximal end of the distalhub into the distal hub. One spline of the plurality of splines may bein each spline channel of the plurality of spline channels of the distalhub. Each spline channel of the plurality of spline channels of thedistal hub may terminate proximal to the distal end of the distal hub.The proximal end of the distal hub may comprise a tapered surface. Thetapered surface of the proximal end of the distal hub may compriseopenings to the plurality of spline channels. The tapered surfaceproximal end of the distal hub may be configured to facilitate bendingof the splines in a radially outward direction. The distal end of thedistal hub may comprise an atraumatic configuration.

The handle may comprise a handle base comprising a proximal end, adistal end, and a lumen extending from the proximal end to the distalend. The handle may further comprise a proximal end of the outer tubecoupled to the lumen of the handle base. The shaft may slidably extendthrough the lumen of the handle base. The handle may further comprise anactuator affixed to a proximal end of the shaft. The actuator may bemoveable relative to the handle base in a proximal direction and in adistal direction. The actuator may be configured to expand theexpandable structure when moved in a distal direction and to compressthe expandable structure when moved in a proximal direction. The handlemay further comprise an outer handle extending from the handle base, asecuring member comprising a proximal end affixed to the actuator, and alocking member positioned along the securing member between the outerhandle and the actuator. The locking member may be configured to bemoved along the longitudinal axis of the securing member and secured ata position along a length of the securing member to inhibit movement ofthe actuator in a distal direction.

The securing member may comprise a threaded shaft and the locking membermay comprise a threaded channel. The locking member may belongitudinally moveable along the securing member by rotating thelocking member around the threaded shaft.

The handle may further comprise a locking member having a lockedconfiguration and an unlocked configuration. The locking member maycomprise a main body comprising a proximal end and a distal end, achannel extending from the proximal end to the distal end, and aprotrusion extending into the channel of the locking member. Theactuator may extend through the channel of the locking member. Theprotrusion may be configured to inhibit the actuator from moving in atleast one of a proximal direction and a distal direction relative to thehandle base when the locking member may be in the locked configuration.The actuator may be moveable in the proximal direction and in the distaldirection when the locking member may be in the unlocked configuration.The actuator may comprise an elongate body, a textured surface along alength of the elongate body of the actuator, and the locking membermoveable between the locked configuration and the unlocked configurationby rotating the locking member around the elongate body of the actuator.The protrusion may be configured to interface with the textured surfacein a locked position and configured to not interface with the texturedsurface in the unlocked position.

The locking member may further comprise a tab extending away from themain body. The tab may be positionable in a first position relative tothe handle base when the locking member is in a locked configuration.The tab may be positionable in a second position when the locking memberis in an unlocked configuration. The textured surface may comprise aseries of ridges. The protrusion of the locking member may be configuredto mate with a notch between the ridges. The channel of the lockingmember may be oblong. The locking member may be configured to switchbetween a locked configuration and an unlocked configuration by rotatingthe locking member a quarter turn.

The handle base further may comprise an aperture in a sidewall extendinginto the lumen of the handle base and proximal to the proximal end ofthe outer tube. An electrical conductor may extend from an electricalsocket into the outer tube through the aperture of the handle base.

The shaft may comprise a lumen. The lumen of the shaft may be configuredto receive a guidewire. A proximal end of the shaft may be configured toreceive fluid. The proximal end of the shaft may be joined to a fluidvalve. The shaft may comprise a sidewall and an aperture in thesidewall. The aperture may be configured to permit fluid to flow out ofthe lumen of the shaft and to the proximal hub.

The device may be configured to transfer fluid injected into the shaftthrough the shaft to the distal hub and through the outer tube to theproximal hub. The shaft may comprise a plurality of hypotubes. Theplurality of hypotubes may comprise a first hypotube having a proximalend and a distal end, and a second hypotube having a proximal end and adistal end. The distal end of the first hypotube may be in the proximalend of the second hypotube. The proximal end of the second hypotube maybe in the distal end of the first hypotube. The plurality of hypotubesmay include three hypotubes. At least one hypotube of the plurality ofhypotubes may comprise a proximal portion having a first outer diameterand a distal portion having a second outer diameter less than the firstouter diameter. At least one hypotube of the plurality of hypotubes maycomprise a sidewall and an aperture through the sidewall.

The device may further comprise an inflatable member. The device mayfurther comprise an inflation lumen in fluid communication with theinflatable member.

In some embodiments, a device comprises, or alternatively consistsessentially of, a handle and an expandable structure. The expandablestructure has a collapsed state and a self-expanded state. Theexpandable structure comprises a plurality of splines extending from aproximal hub to a distal hub. The device further comprises an energydelivery neuromodulator on a first spline of the plurality of splines,an outer tube extending from the handle to the proximal hub, and a shaftextending through the outer tube from the handle to the distal hub, thehandle configured to retract the shaft. The energy deliveryneuromodulator may comprise an electrode. The neuromodulator maycomprise a transducer.

In some embodiments, a device comprises, or alternatively consistsessentially of, a handle and an expandable structure. The expandablestructure has a collapsed state and a self-expanded state. Theexpandable structure comprises a plurality of splines extending from aproximal hub to a distal hub. The device further comprises aneuromodulator on a first spline of the plurality of splines, an outertube extending from the handle to the proximal hub, and a shaftextending through the outer tube from the handle to the distal hub. Thehandle is configured to retract the shaft. The neuromodulator maycomprise a radiofrequency electrode, an ultrasound element, a laserelement, a microwave element, a cryogenic element, a thermal deliverydevice, or a drug delivery device.

Use of the device may be for neuromodulation. Use of the device may befor treatment of a cardiovascular condition. Use of the device may befor treatment of acute heart failure. Use of the device may be fortreatment of shock. Use of the device may be for treatment of valvulardisease. Use of the device may be for treatment of angina. Use of thedevice may be for treatment of microvascular ischemia. Use of the devicemay be for treatment of myocardial contractility disorder. Use of thedevice may be for treatment of cardiomyopathy. Use of the device may befor treatment of hypertension. Use of the device may be for treatment ofpulmonary hypertension. Use of the device may be for treatment ofsystemic hypertension. Use of the device may be for treatment oforthostatic hypertension. Use of the device may be for treatment oforthopnea. Use of the device may be for treatment of dyspenea. Use ofthe device may be for treatment of dysautonomia. Use of the device maybe for treatment of syncope. Use of the device may be for treatment ofvasovagal reflex. Use of the device may be for treatment of carotidsinus hypersensitivity. Use of the device may be for treatment ofpericardial effusion. Use of the device may be for treatment of cardiacstructural abnormalities.

In some embodiments, a method of modulating a nerve comprises, oralternatively consists essentially of, inserting a distal portion of thedevice into vasculature, allowing the expandable member to self-expand,actuating the handle to further expand the expandable structure toanchor the expandable structure in the vasculature, and activating thefirst electrode to stimulate the nerve.

The method may further comprise accessing the vasculature with a needleand a syringe. Accessing the vasculature may be at a jugular vein.Accessing the vasculature may be at a left jugular vein.

The method may further comprise inserting a guidewire into thevasculature. The shaft may comprise a lumen extending from a proximalportion of the device to the distal portion of the device. Inserting thedistal portion of the device into the vasculature may comprise trackingthe device over the guidewire to position the expandable structure at atarget location in the vasculature. The guidewire may slide through thelumen of the shaft.

The method may further comprise inserting a Swan-Ganz cathetercomprising a distal end comprising a balloon into vasculature, inflatingthe balloon, allowing the balloon to be carried by blood flow to thetarget location, inserting the guidewire through a lumen in theSwan-Ganz catheter, deflating the balloon, and retracting the Swan-Ganzcatheter from the vasculature.

The target location may be a pulmonary artery. The target location maybe a right pulmonary artery. The target location may be a pulmonarytrunk. The target location may be a left pulmonary artery.

The method may further comprise inserting an introducer in thevasculature. Inserting the distal portion of the device into thevasculature may comprise inserting the device through a sheath of theintroducer. The method may further comprise at least one of proximallyretracting a distal end of the introducer sheath and distally advancingthe distal portion of the device, allowing the expandable structure toself-expand. The method may further comprise actuating a locking memberon the handle.

The nerve may comprise a cardiopulmonary nerve. The nerve may comprise aright dorsal medial CPN. The nerve may comprise a right dorsal lateralCPN. The nerve may comprise a right stellate CPN. The nerve may comprisea right vagal nerve or vagus. The nerve may comprise a right cranialvagal CPN. The nerve may comprise a right caudal vagal CPN. The nervemay comprise a right coronary cardiac nerve. The nerve may comprise aleft coronary cardiac nerve. The nerve may comprise a left lateralcardiac nerve. The nerve may comprise a left recurrent laryngeal nerve.The nerve may comprise a left vagal nerve or vagus. The nerve maycomprise a left stellate CPN. The nerve may comprise a left dorsallateral CPN. The nerve may comprise a left dorsal medial CPN.

The method may comprise positioning the expandable structure againsttissue in the vasculature so that the nerve is between the firstelectrode and a second electrode.

Activating the first electrode may comprise applying a voltage pulsehaving a first polarity. The method may further comprise, beforeactivating the first electrode, applying a pre-pulse of voltage totissue surrounding the nerve. The pre-pulse may have a second polarityopposite the first polarity.

The method may further comprise measuring pressure in a right ventricleand approximating pressure in the left ventricle from the pressuremeasured in the right ventricle.

The method may further comprise positioning a return conductor in thevasculature. The return conductor may be configured to conduct currentfrom an activated electrode.

A current vector from the first electrode to the return electrode may beaway from at least one of a heart and a trachea. Positioning the returnconductor in the vasculature may comprise positioning the returnelectrode at least 5 mm away from the first electrode. Positioning thereturn conductor in the vasculature may comprise positioning the returnelectrode in a right ventricle. Positioning the return conductor in thevasculature may comprise positioning the return electrode a superiorvena cava. Positioning the return conductor in the vasculature maycomprise positioning the return electrode a brachiocephalic vein.

The methods summarized above and set forth in further detail belowdescribe certain actions taken by a practitioner; however, it should beunderstood that they can also include the instruction of those actionsby another party. Thus, actions such as “positioning an electrode”include “instructing positioning of an electrode.”

For purposes of summarizing the invention and the advantages that may beachieved, certain objects and advantages are described herein. Notnecessarily all such objects or advantages need to be achieved inaccordance with any particular embodiment. In some embodiments, theinvention may be embodied or carried out in a manner that can achieve oroptimize one advantage or a group of advantages without necessarilyachieving other objects or advantages.

The embodiments disclosed herein are intended to be within the scope ofthe invention herein disclosed. These and other embodiments will beapparent from the following detailed description having reference to theattached figures, the invention not being limited to any particulardisclosed embodiment(s). Optional and/or preferred features describedwith reference to some embodiments may be combined with and incorporatedinto other embodiments. All references cited herein, including patentsand patent applications, are incorporated by reference in theirentirety.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 schematically illustrates a system that can be used to applyelectrical neuromodulation to one or more nerves in and around the heartof a subject.

FIG. 2A schematically illustrates a heart and surrounding areas.

FIGS. 2B-2D are schematic illustrations of a heart and surrounding areasfrom various perspectives.

FIGS. 2E and 2F are schematic illustrations of a heart and surroundingnerves.

FIGS. 2G and 2H are schematic illustrations of vasculature and anelectrode matrix.

FIG. 2I is a schematic illustration of heart vasculature and surroundingnerves.

FIG. 2J is a schematic illustration of vasculature and surroundingnerves.

FIG. 2K is another schematic illustration of a heart and surroundingnerves.

FIG. 2L illustrates an example stimulation device.

FIG. 3A is a side perspective and partial cross-sectional view of anexample of a catheter.

FIG. 3B is a distal end view of the catheter of FIG. 3A as viewed alongline 3B-3B in FIG. 3A.

FIG. 4A is a side perspective and partial cross-sectional view ofanother example of a catheter.

FIG. 4B is a distal end view of the catheter of FIG. 4A as viewed alongline 4B-4B in FIG. 4A.

FIG. 4C is a side perspective view of an example of a portion of acatheter.

FIGS. 5 and 6 illustrate examples of catheters.

FIGS. 7A and 7B illustrate embodiments of a pulmonary artery catheterthat can be used with the catheters according to the present disclosure.

FIGS. 8A and 8B illustrate examples of catheters.

FIG. 8C illustrates the catheter of FIG. 8A positioned within the mainpulmonary artery.

FIG. 8D illustrates the catheter of FIG. 8B positioned within the mainpulmonary artery.

FIGS. 9 and 10 illustrate additional examples of catheters.

FIG. 11 illustrates an example of a catheter system.

FIG. 12A-12D illustrate various examples of catheters.

FIG. 13 is a perspective view of a catheter positioned in a heart of apatient.

FIGS. 14A, 14B, 15A, 15B, 16 and 17 illustrate examples of catheters.

FIGS. 18A through 18C are side partial cross-sectional and perspectiveviews of an example catheter that is suitable for performing the methodsof the present disclosure.

FIG. 18D illustrates the catheter of FIGS. 18A through 18C positioned inthe right pulmonary artery of a heart.

FIG. 19 is partial cross-sectional and perspective view of an examplecatheter positioned in a heart of a patient.

FIG. 20 is a side partial cross-sectional and perspective view of anexample first catheter and an example second catheter that are suitablefor performing the methods of the present disclosure.

FIG. 21 illustrates an embodiment of a stimulation system for use withthe catheters or catheter systems of the present disclosure.

FIG. 22A is a perspective view of an example of a portion of a catheter.

FIG. 22B is a side elevational view of the portion of FIG. 22A.

FIG. 22C is a distal end view of the portion of FIG. 22A.

FIG. 22D is a proximal end view of the portion of FIG. 22A.

FIGS. 22E-22G are side partial cross-sectional views of an example of acatheter including the portion of FIG. 22A.

FIGS. 22H-22L are side elevational and partial cross-sectional views ofexamples of catheter deployment systems.

FIG. 22M illustrates an example part of the portion of FIG. 22A.

FIG. 23A is a perspective view of an example segment of a strut.

FIG. 23B is a transverse cross-sectional view of an example of a strut.

FIG. 23C is a transverse cross-sectional view of an example of a strut.

FIG. 23D is a transverse cross-sectional view of another example of astrut.

FIG. 23E is a transverse cross-sectional view of yet another example ofa strut.

FIG. 23F is a transverse cross-sectional view of still another exampleof a strut.

FIG. 23G is a top partial cross-sectional view of an example segment ofa strut.

FIG. 23H illustrates an example of a strut system.

FIG. 23I shows an example in which a distance between a first strut anda second strut is less than a distance a between a third strut and thesecond strut.

FIG. 23J shows an example in which a distance between a first strut anda second strut is substantially the same as a distance a between a thirdstrut and the second strut.

FIG. 23K illustrates an example of an electrode on wire system.

FIG. 23L is a cross-sectional view of an electrode spaced from a vesselwall.

FIG. 23M shows an example electrode matrix.

FIGS. 23Ni-23Nix illustrate an example method of manufacturingcomponents on a substrate.

FIG. 24A illustrates an example of a fixation system.

FIGS. 24B and 24C illustrate the fixation system of FIG. 24A interactingwith a catheter.

FIG. 25A is a perspective view of another example of a fixation system.

FIG. 25B is a side elevational view of the fixation system of FIG. 25A.

FIG. 25C is an end view of the fixation system of FIG. 25A.

FIGS. 25D and 25E illustrate the fixation system of FIG. 25A interactingwith a catheter.

FIG. 25F illustrates an example of a catheter comprising a shaped lumen.

FIGS. 25G-25J illustrate an example deployment out of the lumen of thecatheter of FIG. 25F.

FIG. 26A is a side elevational view of an example of a catheter system2600.

FIGS. 26B-26H illustrate an example method of deploying the cathetersystem 2600 of FIG. 26A.

FIG. 27A is a perspective view of another example of a fixation system.

FIG. 27B is an elevational view of a portion of the fixation system ofFIG. 27A.

FIGS. 27C-27F illustrate the fixation system of FIG. 27A being retractedafter engagement with tissue.

FIG. 27G is a perspective view of yet another example of a fixationsystem.

FIG. 27H is a side view of the fixation system of FIG. 27G.

FIG. 27I is a side view of still another example of a fixation system.

FIG. 28A is a side view of an example of a fixation system.

FIG. 28B is an expanded view of the dashed circle 28B in FIG. 28A.

FIG. 28C is an expanded view of the dotted square 28C in FIG. 28A.

FIG. 28D shows an example of a radiopaque marker coupled to a proximalfixation mechanism.

FIG. 28E shows an example of a hole in a proximal fixation mechanism.

FIG. 28F is a flattened view of an example of a hypotube cut pattern.

FIG. 28G is an expanded view of the dashed square 28G in FIG. 28F.

FIG. 28H is a side view of the strut of FIG. 28G.

FIG. 28I is a side view of a proximal fixation mechanism being bentradially outward.

FIG. 28J is a side view of a proximal fixation mechanism being bentradially outward and a strut being bent at a bend point.

FIG. 28K is a side view of a strut being bent at a bend point.

FIGS. 28L-28O show proximal fixation mechanisms rotating inwardly duringretrieval into a catheter.

FIG. 29A illustrates an example of a catheter system.

FIGS. 29B-29F illustrate an example method of deploying the cathetersystem of FIG. 29A.

FIG. 29G illustrates an example of a catheter system.

FIG. 29H illustrates another example of a catheter system.

FIG. 29I illustrates yet another example of a catheter system.

FIG. 29J illustrates still another example of a catheter system.

FIG. 29K illustrates yet still another example of a catheter system.

FIGS. 29L-29N illustrate an example method of deploying the cathetersystem of FIG. 29K.

FIG. 30A is a perspective view of an example of an electrode system.

FIG. 30B is a top plan view of a portion of the electrode system of FIG.30A.

FIG. 30C is a perspective view of another example of an electrodesystem.

FIG. 30D is a distal end view of the electrode system of FIG. 30C in acollapsed state.

FIG. 30E is a distal end view of the electrode system of FIG. 30C in anexpanded state.

FIG. 30F is a plan view of yet another example of an electrode system.

FIG. 30G is a distal end view of the electrode system of FIG. 30F.

FIGS. 31A and 31B show example electrode combinations for nineelectrodes in a 3×3 matrix.

FIGS. 32A-32D show example electrode combinations for twelve electrodesin a 3×4 matrix.

FIG. 33A is a plot of contractility versus stimulation.

FIG. 33B is another plot of contractility versus stimulation.

FIG. 34 is an example process flow that can be used to implement a dutycycle method.

FIG. 35A schematically illustrates a mechanically repositionableelectrode catheter system.

FIG. 35B illustrates the catheter system of FIG. 35A after longitudinaladvancement.

FIG. 35C illustrates the catheter system of FIG. 35A after longitudinaladvancement and rotation.

FIG. 35D is a cross-sectional view taken along the line 35D-35D of FIG.35C.

FIG. 36A is a perspective view of an example of a catheter system.

FIG. 36B is a perspective view of a portion of the catheter system ofFIG. 36A in a collapsed state.

FIG. 36C is a side view of a portion of the catheter system of FIG. 36Ain an expanded state.

FIG. 36D schematically illustrates a side view of an example of anexpandable structure.

FIG. 36E schematically illustrates a side view of another example of anexpandable structure.

FIG. 36F schematically illustrates a side view of still another exampleof an expandable structure.

FIG. 36G schematically illustrates a perspective view of yet anotherexample of an expandable structure.

FIG. 36H schematically illustrates an example of an expandable structurepattern.

FIG. 36I schematically illustrates another example of an expandablestructure pattern.

FIG. 36J schematically illustrates still another example of anexpandable structure pattern.

FIG. 36K schematically illustrates yet another example of an expandablestructure pattern.

FIG. 36L schematically illustrates still yet another example of anexpandable structure pattern.

FIG. 36M schematically illustrates another example of an expandablestructure pattern.

FIG. 36N schematically illustrates an example of an expandablestructure.

FIG. 36O schematically illustrates an example of an expandable structurepattern.

FIG. 36P schematically illustrates a side view of an example of anexpandable structure.

FIG. 36Q is a proximal end view of the expandable structure of FIG. 36P.

FIG. 37A is a perspective view of an example of a catheter system.

FIG. 37B is a side view of an example of an expandable structure.

FIG. 37C is a proximal end view of the expandable structure of FIG. 37B.

FIG. 37D is a perspective view of a wire bent to form a spline pair.

FIG. 37E is a perspective view of a spline pair comprising electrodes.

FIG. 37F is an expanded perspective view of the distal end of the splinepair of FIG. 37E.

FIG. 37Fi-37Fiii illustrate an example of electrical movement ofelectrodes.

FIG. 37G is a perspective view of an example of a proximal hub of anexpandable structure.

FIG. 37H schematically illustrates a side cross-sectional view of theproximal hub of FIG. 37G.

FIG. 37I is a perspective view of a distal end of the proximal hub ofFIG. 37G.

FIG. 37J schematically illustrates a side cross-sectional view of anexample of a distal hub of an expandable structure.

FIG. 37K is a side view of an example of a proximal end of the cathetersystem of FIG. 37A.

FIG. 37L is a side cross-sectional view of the proximal end of FIG. 37K.

FIGS. 37Li-37Liii show an example method of operating a handle toradially expand an expandable member.

FIGS. 37Li and 37Liv show another example method of operating a handleto radially expand an expandable member.

FIG. 37M is a side cross-sectional view of example components of ahandle base.

FIG. 37N is a perspective view of a proximal end of an example of acatheter shaft assembly and support tube.

FIG. 37O is a side cross-sectional view of an example connection betweena distal end of a catheter shaft assembly and a proximal hub of anexpandable structure.

FIG. 37P is a perspective view of an end of an example of a hinge.

FIG. 37Q is a perspective view of an example handle of a catheter systemin an unlocked configuration.

FIG. 37R schematically illustrates a perspective cross-sectional view ofthe handle of FIG. 37Q along the line 37R-37R.

FIG. 37S is a perspective view of an example of a locking member.

FIG. 37T schematically illustrates an expanded perspectivecross-sectional view of the handle of FIG. 37Q in an unlockedconfiguration in the area of the circle 37T of FIG. 37R.

FIG. 37U is a perspective view of the handle of FIG. 37Q in a lockedconfiguration.

FIG. 37V schematically illustrates a perspective cross-sectional view ofthe handle of FIG. 37U along the line 37V-37V.

FIG. 38A is a perspective view of an example of a catheter system.

FIG. 38B is a perspective view of a portion of the catheter system ofFIG. 38A in a collapsed state.

FIG. 38C is a side view of a portion of the catheter system of FIG. 38Ain an expanded state.

FIG. 38D is a partial side cross-sectional view of an expandablestructure.

FIG. 38E is a partial side cross-sectional view of an expandablestructure.

FIG. 39A is a side view of an example of an expandable structure.

FIG. 39B is an end view of an example of another expandable structure.

FIG. 39C is an end view of an example of yet another expandablestructure.

FIG. 39D is an end view of an example of still another expandablestructure.

FIG. 40A is a perspective view of an example of a strain relief for acatheter system.

FIG. 40B is a perspective view of another example of a strain relief fora catheter system.

FIG. 41A is a perspective view of an example of a catheter system.

FIG. 41B is a perspective view of a portion of the catheter system ofFIG. 41A in a collapsed and deflated state.

FIG. 41C is a transverse cross-sectional side view of the portion ofFIG. 41B.

FIG. 41D is a side view of the portion of FIG. 41B in an inflated state.

FIG. 41E is a perspective view of the portion of FIG. 41B in an expandedstate.

FIG. 41F schematically illustrates an expandable structure expanded invasculature.

FIG. 41G schematically illustrates yet another example of an expandablestructure expanded in vasculature.

FIG. 42A is a side view of an example of an electrode structure.

FIG. 42B is a side view of another example of an electrode structure.

FIG. 43A is a side view of an example of an electrode.

FIG. 43B is a side view of another example of an electrode.

FIG. 44A is a side view of an example of an electrode.

FIG. 44B is a side view of another example of an electrode.

FIG. 45 is a diagram of neurostimulation of a nerve proximate to avessel wall.

FIG. 46A is a graph showing the monitoring of left ventriclecontractility and right ventricle contractility over time.

FIG. 46B is another graph showing the monitoring of left ventriclecontractility and right ventricle contractility over time.

FIG. 47A schematically illustrates an example electrocardiograph.

FIG. 47B is an example of a modified electrocardiograph.

FIG. 47C is an example of a monitored electrocardiograph.

FIG. 47D is an example of a modified electrocardiograph.

FIG. 47E is another example of a modified electrocardiograph.

FIG. 47F is still another example of a modified electrocardiograph.

FIG. 47G is yet another example of a modified electrocardiograph.

FIG. 48A illustrates insertion of a needle into vasculature.

FIG. 48B illustrates insertion of an introducer and guidewire intovasculature.

FIG. 48C illustrates a Swan-Ganz catheter and guidewire positioned inthe right pulmonary artery.

FIG. 48D illustrates an example catheter system positioned in the rightpulmonary artery in an expanded state.

FIG. 48E illustrates the catheter system of FIG. 48D in a furtherexpanded state.

FIG. 48F is a side view of a portion of a catheter system inserted intoan introducer.

FIG. 48G is a fluoroscopic image of the catheter system positioned inthe right pulmonary artery.

FIG. 48H schematically illustrates stimulation of a target nerve by theelectrodes of a catheter system positioned in the right pulmonaryartery.

DETAILED DESCRIPTION

Several embodiments of the present disclosure provide for methods anddevices that can be used to apply electrical neuromodulation to one ormore nerves in and around the heart of a subject (e.g., patient).Several embodiments, for example, may be useful in electricalneuromodulation of patients with cardiovascular medical conditions, suchas patients with acute or chronic cardiac disease. As discussed herein,several embodiments can allow for a portion of a catheter to bepositioned within the vasculature of the patient in at least one of theright pulmonary artery, the left pulmonary artery, and the pulmonarytrunk. Once positioned, an electrode system of the catheter can provideelectrical energy (e.g., electrical current or electrical pulses) tostimulate the autonomic nervous system surrounding (e.g., proximate to)the pulmonary artery in an effort to provide adjuvant cardiac therapy tothe patient. Sensed heart activity properties (e.g., non-electricalheart activity properties) can be used as the basis for makingadjustments to one or more properties of the one or more electricalpulses delivered through the catheter positioned in the pulmonary arteryof the heart in an effort to provide adjuvant cardiac therapy to thepatient.

Certain groups of figures showing similar items follow a numberingconvention in which the first digit or digits correspond to the drawingfigure number and the remaining digits identify an element or componentin the drawing. Similar elements or components between such groups offigures may be identified by the use of similar digits. For example, 336may reference element “36” in FIG. 3A, and a similar element “36” may bereferenced as 436 in FIG. 4A. As will be appreciated, elements shown inthe various embodiments herein can be added, exchanged, and/oreliminated so as to provide any number of additional embodiments of thepresent disclosure. Components or features described in connection witha previous figure may not be described in detail in connection withsubsequent figures; however, the embodiments illustrated in thesubsequent figures may include any of the components or combinations ofcomponents or features of the previous embodiments.

The terms “distal” and “proximal” are used herein with respect to aposition or direction relative to the treating clinician taken along thedevices of the present disclosure. “Distal” or “distally” are a positiondistant from or in a direction away from the clinician taken along thecatheter. “Proximal” and “proximally” are a position near or in adirection toward the clinician taken along the catheter.

The catheter and electrode systems of the present disclosure can be usedto treat a patient with various cardiac conditions. Such cardiacconditions include, but are not limited to, acute heart failure, amongothers. Several embodiments of the present disclosure provides methodsthat can be used to treat acute heart failure, also known asdecompensated heart failure, by modulating the autonomic nervous systemsurrounding the pulmonary artery (e.g., the right pulmonary artery, theleft pulmonary artery, the pulmonary trunk) in an effort to provideadjuvant cardiac therapy to the patient. The neuromodulation treatmentcan help by affecting heart contractility more than heart rate. In apreferred embodiment, the autonomic nervous system is modulated so as tocollectively affect heart contractility more than heart rate. Theautonomic nervous system can be impacted by electrical modulation thatincludes stimulating and/or inhibiting nerve fibers of the autonomicnervous system.

As discussed herein, the one or more electrodes present on the cathetercan be positioned within the main pulmonary artery and/or one or both ofthe right and left pulmonary arteries. In accordance with severalembodiments, the one or more electrodes are positioned in contact theluminal surface of the main pulmonary artery, and/or right or leftpulmonary artery (e.g., in physical contact with the surface of theposterior portion of the main pulmonary artery). As will be discussedherein, the one or more electrodes on the catheter and/or cathetersystem provided herein can be used to provide pulse of electrical energybetween the electrodes and/or the reference electrodes. The electrodesof the present disclosure can be used in any one of a unipolar, bi-polarand/or a multi-polar configuration. Once positioned, the catheter andthe catheter system of the present disclosure can provide thestimulation electrical energy to stimulate the nerve fibers (e.g.,autonomic nerve fibers) surrounding the main pulmonary artery and/or oneor both of the right and left pulmonary arteries in an effort to provideadjuvant cardiac therapy to the patient (e.g., electrical cardiacneuromodulation).

In some embodiments, systems other than intravascular catheters may beused in accordance with the methods described herein. For example,electrodes, sensors, and the like may be implanted during open heartsurgery or without being routed through vasculature.

Several embodiments, as will be discussed more fully herein, may allowfor the electrical neuromodulation of the heart of the patient thatincludes delivering one or more electrical pulses through a catheterpositioned in a pulmonary artery of the heart of the patient, sensingfrom at least a first sensor positioned at a first location within thevasculature of the heart one or more heart activity properties (e.g.,non-electrical heart activity properties) in response to the one or moreelectrical pulses, and adjusting a property of the one or moreelectrical pulses delivered through the catheter positioned in thepulmonary artery of the heart in response to the one or more heartactivity properties in an effort to provide adjuvant cardiac therapy tothe patient.

The catheter can include a plurality of electrodes, which are optionallyinserted into the pulmonary trunk, and positioned such that theelectrodes are, preferably, in contact with the posterior surface, thesuperior surface, and/or the inferior surface of the pulmonary artery.From such locations, electrical pulses can be delivered to or from theelectrodes to selectively modulate the autonomic nervous system of theheart. For example, electrical pulses can be delivered to or from one ormore of the electrodes to selectively modulate the autonomiccardiopulmonary nerves of the autonomic nervous system, which canmodulate heart contractility more than heart rate. Preferably, theplurality of electrodes is positioned at a site along the posterior walland/or superior wall of the pulmonary artery, for example the right orleft pulmonary artery. From such a position in the pulmonary artery, oneor more electrical pulses can be delivered through the electrodes andone or more heart activity properties (e.g., non-electrical heartactivity properties) can be sensed. Based at least in part on thesesensed heart activity properties, a property of the one or moreelectrical pulses delivered to or from the electrodes positioned in thepulmonary artery of the heart can be adjusted in an effort to positivelyinfluence heart contractility while reducing or minimizing the effect onheart rate and/or oxygen consumption. In certain embodiments, the effecton heart contractility is to increase heart contractility.

FIG. 1 schematically illustrates a system 100 that can be used to applyelectrical neuromodulation to tissue (e.g., including one or morenerves) in and around the heart of a subject. The system 100 comprises afirst component 102 and a second component 104. The first component 102may be positioned in a pulmonary artery (e.g., the right pulmonaryartery as shown in FIG. 1 , the left pulmonary artery, and/or thepulmonary trunk). The first component 102 may be endovascularlypositioned via a minimally invasive, transdermal, percutaneousprocedure, for example routed through the vasculature from a remotelocation such as a jugular vein (e.g., an internal jugular vein, asshown in FIG. 1 ), an axial subclavian vein, a femoral vein, or otherblood vessels. Such an approach can be over-the-wire, using a Swan-Ganzfloat catheter, combinations thereof, etc. In some embodiments, thefirst component may be positioned invasively, for example duringconventional surgery (e.g., open-heart surgery), placement of anotherdevice (e.g., coronary bypass, pacemaker, defibrillator, etc.), or as astand-alone procedure. As described in further detail herein, the firstcomponent comprises a neuromodulator (e.g., electrode, transducer, drug,ablation device, ultrasound, microwave, laser, cryo, combinationsthereof, and the like) and may optionally comprise a stent or framework,an anchoring system, and/or other components. The first component 102may be acutely positioned in the pulmonary artery for 24 to 72 hours. Insome embodiments, the first component 102 neuromodulates terminalbranches within the cardiac plexus, which can increase left ventriclecontractility. The increase in left ventricle contractility may bewithout an increase in heart rate or may be greater than (e.g., based ona percentage change) than an increase in heart rate. In someembodiments, the first component 102 may be adapted to ablate tissue,including nerves, in addition to or instead of modulating tissue such asnerves.

The first component 102 is electrically coupled to the second component104 (e.g., via wires or conductive elements routed via a catheter, forexample as illustrated in FIG. 1 , and/or wirelessly). The secondcomponent 104 may be positioned extracorporeally (e.g., strapped to asubject's arm as shown in FIG. 1 , strapped to another part of thesubject (e.g., leg, neck, chest), placed on a bedside stand, etc.). Insome embodiments, the second component 104 may be temporarily implantedin the subject (e.g., in a blood vessel, in another body cavity, in achest, etc.). The second component 104 includes electronics (e.g., pulsegenerator) configured to operate the electrode in the first component102. The second component 104 may include a power supply or may receivepower from an external source (e.g., a wall plug, a separate battery,etc.). The second component 104 may include electronics configured toreceive sensor data.

The system 100 may comprise a sensor. The sensor may be positioned inone or more of a pulmonary artery (e.g., right pulmonary artery, leftpulmonary artery, and/or pulmonary trunk), an atrium (e.g., right and/orleft), a ventricle (e.g., right and/or left), a vena cava (e.g.,superior vena cava and/or inferior vena cava), and/or othercardiovascular locations. The sensor may be part of the first component102, part of a catheter, and/or separate from the first component 102(e.g., electrocardiogram chest monitor, pulse oximeter, etc.). Thesensor may be in communication with the second component 104 (e.g.,wired and/or wireless). The second component 104 may initiate, adjust,calibrate, cease, etc. neuromodulation based on information from thesensor.

The system 100 may comprise an “all-in-one” system in which the firstcomponent 102 is integral or monolithic with the targeting catheter. Forexample, the first component 102 may be part of a catheter that isinserted into an internal jugular vein, an axial subclavian vein, afemoral vein, etc. and navigated to a target location such as thepulmonary artery. The first component 102 may then be deployed from thecatheter. Such a system can reduce the number and/or complexity ofprocedural steps and catheter exchanges used to position the firstcomponent 102. For example, a guidewire may be at least twice as long asa target catheter, which can be difficult to control in a sterile field.Such a system may make repositioning of the first component 102 easierafter an initial deployment because positioning systems are already inplace.

The system 100 may comprise a telescoping and/or over-the-wire system inwhich the first component 102 is different than the targeting catheter.For example, a targeting catheter (e.g., a Swan-Ganz catheter) may beinserted into an internal jugular vein, an axial subclavian vein, afemoral vein, etc. and navigated to a target location such as thepulmonary artery (e.g., by floating). A guidewire may be inserted into aproximal hub through the target catheter to the target location (e.g.,having a stiffest portion exiting the target catheter distal end) andthe first component 102 as part of a separate catheter than the targetcatheter may be tracked to the target location over the guidewire orusing telescoping systems such as other guidewires, guide catheters,etc. The first component 102 may then be deployed from the separatecatheter. Such systems are known by interventional cardiologists suchthat multiple exchanges may be of little issue. Such a system may allowcustomization of certain specific functions. Such a system may reduceoverall catheter diameters, which can increase trackability, and/orallow additional features to be added, for example because not allfunctions are integrated into one catheter. Such a system may allow useof multiple catheters (e.g., removing a first separate catheter andpositioning a second separate catheter without having to reposition theentire system). For example, catheters with different types of sensorsmay be positioned and removed as desired. The system 100 may besteerable (e.g., comprising a steerable catheter) without a Swan-Ganztip. Some systems 100 may be compatible with one or more of thedescribed types of systems (e.g., a steerable catheter with anoptionally inflatable balloon for Swan-Ganz float, a steerable catheterthat can be telescoped over a guidewire and/or through a catheter,etc.).

FIG. 2A schematically illustrates a heart 200 and surrounding areas. Themain pulmonary artery or pulmonary trunk 202 begins at the outlet of theright ventricle 204. In an adult, the pulmonary trunk 202 is a tubularstructure having a diameter of about 3 centimeter (cm) (approx. 1.2inches (in)) and a length of about 5 (approx. 2.0 in). The mainpulmonary artery 202 branches into the right pulmonary artery 206 andthe left pulmonary artery 208, which deliver deoxygenated blood to thecorresponding lung. As illustrated in FIG. 2A, the main pulmonary artery202 has a posterior surface 210 that arches over the left atrium 212 andis adjacent to the pulmonary vein 213. As discussed herein, aneurostimulator can be positioned at least partially in a pulmonaryartery 202, 206, 208, for example with the neurostimulator in contactwith the posterior surface 210. In some embodiments, a preferredlocation for positioning the neurostimulator is the right pulmonaryartery 204. PCT Patent App. No. PCT/US2015/047780 and U.S. ProvisionalPatent App. No. 62/047,313 are incorporated herein by reference in theirentirety, and more specifically the descriptions of positioning in theright pulmonary artery disclosed therein are incorporated herein byreference. In some embodiments, a preferred location for positioning theneurostimulator is in contact with the posterior surface 210 of thepulmonary artery 202, 206, 208. From such a location, stimulationelectrical energy delivered from an electrode, for example, may bebetter able to treat and/or provide therapy (including adjuvant therapy)to a subject experiencing a variety of cardiovascular medicalconditions, such as acute heart failure. Other locations for theneurostimulator in the pulmonary artery 202, 206, 208 are also possible.

The first component 102 (FIG. 1 ) can be positioned in the pulmonaryartery 202, 206, 208 of the subject, where the neurostimulator of thefirst component 102 is in contact with the luminal surface of thepulmonary artery 202, 206, 208 (e.g., in physical contact with orproximate to the surface of the posterior portion 210 of the pulmonaryartery 202, 206, 208). The neurostimulator of the first component 102can be used to deliver the stimulation to the autonomic cardiopulmonaryfibers surrounding the pulmonary artery 202, 206, 208. The stimulationelectrical energy can elicit responses from the autonomic nervous systemthat may help to modulate a subject's cardiac contractility. Thestimulation may affect contractility more than the heart rate, which canimprove hemodynamic control while possibly reducing unwanted systemiceffects.

In some embodiments, neuromodulation of targeted nerves or tissue asdescribed herein can be used for the treatment of arrhythmia, atrialfibrillation or flutter, diabetes, eating disorders, endocrine diseases,genetic metabolic syndromes, hyperglycemia (including glucosetolerance), hyperlipidemia, hypertension, inflammatory diseases, insulinresistance, metabolic diseases, obesity, ventricular tachycardia,conditions affecting the heart, and/or combinations thereof.

FIGS. 2B-2D are schematic illustrations of a heart 200 and surroundingareas from various perspectives. Portions of the heart 200 (e.g., theaorta, the superior vena cava, among other structures), including aportion of the pulmonary trunk 202, have been removed to allow for thedetails discussed herein to be shown. FIG. 2B provides a perspectiveview of the heart 200 as seen from the front of the subject or patient(viewed in an anterior to posterior direction), while FIG. 2C provides aperspective view of the heart 200 as seen from the right side of thesubject. As illustrated, the heart 100 includes the pulmonary trunk 102that begins at the base of the right ventricle 104. In an adult, thepulmonary trunk 102 is a tubular structure approximately 3 centimeters(cm) in diameter and 5 cm in length. The pulmonary trunk 202 branchesinto the right pulmonary artery 206 and the left pulmonary artery 208 ata branch point or bifurcation 207. The left pulmonary artery 106 and theright pulmonary artery 108 serve to deliver de-oxygenated blood to eachcorresponding lung.

The branch point 207 includes a ridge 209 that extends from theposterior of the pulmonary trunk 202. As illustrated, the branch point207, along with the ridge 209, provides a “Y” or “T” shaped structurethat helps to define at least a portion of the left pulmonary artery 208and the right pulmonary artery 206. For example, from the ridge 209, thebranch point 207 of the pulmonary trunk 202 slopes in oppositedirections. In a first direction, the pulmonary trunk 202 transitionsinto the left pulmonary artery 208, and in the second direction,opposite the first direction, the pulmonary trunk 202 transitions intothe right pulmonary artery 206. The branch point 207 may not necessarilybe aligned along a longitudinal center line 214 of the pulmonary trunk202.

As illustrated in FIG. 2B, portions of the pulmonary artery 202 can bedefined with a right lateral plane 216 that passes along a right luminalsurface 218 of the pulmonary trunk 202, a left lateral plane 220parallel with the right lateral plane 216, where the left lateral plane220 passes along a left luminal surface 222 of the pulmonary trunk 202.The right lateral plane 216 and the left lateral plane 220 extend inboth a posterior direction 224 and anterior direction 226. Asillustrated, the ridge 209 of the branch point 207 is located betweenthe right lateral plane 216 and the left lateral plane 220. The branchpoint 207 is positioned between the right lateral plane 216 and the leftlateral plane 220, where the branch point 207 can help to at leastpartially define the beginning of the left pulmonary artery 208 and theright pulmonary artery 206 of the heart 200. The distance between theright lateral plane 216 and the left lateral plane 220 is approximatelythe diameter of the pulmonary trunk 202 (e.g., about 3 cm).

As discussed herein, the present disclosure includes methods forneuromodulation of the heart 200 of a subject or patient. For example,as discussed herein, a catheter positioned in the pulmonary artery 202can be used to deliver one or more electrical pulses to the heart 200. Afirst sensor, for example as discussed herein, positioned at a firstlocation within the vasculature of the heart 200, senses a heartactivity property in response to the neurostimulation. Properties of theneurostimulator can be adjusted in response to the sensed heart activityproperty in an effort to provide adjuvant cardiac therapy to thepatient.

FIG. 2D provides an additional illustration the posterior surface 221,the superior surface 223, and the inferior surface 225 of the rightpulmonary artery 206. As illustrated, the view of the heart 200 in FIG.2D is from the right side of the heart 200. As illustrated, theposterior surface 221, the superior surface 223, and the inferiorsurface 225 account for approximately three quarters of the luminalperimeter of the right pulmonary artery 206, where the anterior surface227 accounts for the remainder. FIG. 2D also illustrates the aorta 230,pulmonary veins 213, the superior vena cava (SVC) 232, and the inferiorvena cava (IVC) 234.

FIGS. 2E and 2F are schematic illustrations of a heart 200 andsurrounding nerves. The cardiovascular system is richly innervated withautonomic fibers. Sympathetic fibers originate from stellate andthoracic sympathetic ganglia, and are responsible for increases in thechronotropic (heart rate), lusotropic (relaxation), and inotropic(contractility) state of the heart. Human cadaver anatomical studiesshow that the fibers responsible for the lusotropic and inotropic stateof the ventricles pass along the posterior surface of the rightpulmonary artery 206 and the pulmonary trunk 202. FIG. 2E illustratesapproximate positions of the right dorsal medial common peroneal nerve(CPN) 240, the right dorsal lateral CPN 242, the right stellate CPN 244,the right vagal nerve or vagus 246, the right cranial vagal CPN 248, theright caudal vagal CPN 250, the right coronary cardiac nerve 252, theleft coronary cardiac nerve 254, the left lateral cardiac nerve 256, theleft recurrent laryngeal nerve 258, the left vagal nerve or vagus 260,the left stellate CPN 262, the left dorsal lateral CPN 264, and the leftdorsal medial CPN 266. These and/or other nerves surrounding (e.g.,proximate to) the heart 200 can be targeted for neurostimulation by thesystems and methods described herein. In some embodiments, at least oneof the right dorsal medial common peroneal nerve 240, the right stellateCPN 244, and the left lateral cardiac nerve 256 is targeted and/oraffected for neuromodulation, although other nerves, shown in FIG. 2E orotherwise, may also be targeted and/or affected.

FIGS. 2E and 2F also schematically illustrate the trachea 241. As bestseen in FIG. 2F, the trachea 241 bifurcates into the right pulmonarybronchus 243 and the left pulmonary bronchus 241. The bifurcation of thetrachea 241 can be considered along a plane 245. The plane 245 is alongthe right pulmonary artery 206. The bifurcation of the pulmonary arterycan be considered along a plane 247, which is spaced from the plane 245by a gap 249. The gap 249 spans the right pulmonary artery 206. A largenumber of cardiac nerves cross the right pulmonary artery 206 along thegap 249 as illustrated by the circled area 251, and these nerves may beadvantageously targeted by some of the systems and methods describedherein. In certain such embodiments, the bifurcation of the trachea 241and/or the bifurcation of the pulmonary artery 202 may provide alandmark for system and/or component positioning. Stimulation electrodesmay be spaced from the trachea 241, for example to reduce cough or otherpossible respiratory side effects. In some embodiments, stimulationelectrodes are spaced from the trachea 241 or the plane 245 by betweenabout 2 mm and about 8 mm (e.g., about 2 mm, about 3 mm, about 4 mm,about 5 mm, about 6 mm, about 7 mm, about 8 mm, ranges between suchvalues, etc.). In some embodiments, stimulation electrodes are spacedfrom the trachea 241 or the plane 245 by a percentage of a length of theright pulmonary artery 206 between about 10% and about 100% (e.g., about10%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%,about 55%, about 75%, about 100%, ranges between such values, etc.).

FIGS. 2G and 2H are schematic illustrations of vasculature and anelectrode matrix 201. A majority of the electrode matrix 201 ispositioned in the right pulmonary artery 206, although some of theelectrode matrix 201 may be considered positioned in the pulmonary trunk202. The electrode array is shown as a 4×5 matrix of electrodes 203. Asdescribed in further detail herein, the electrodes 203 may be positionedon splines, positioned on a membrane or mesh coupled to splines, etc.For example, four splines may each contain five electrodes 203. In someembodiments, the electrodes 203 comprise bipolar electrodes withcontrollable polarity, allowing configurability of the electrode matrix201. In some embodiments, edge-to-edge spacing of the electrodes 203 isbetween about 3 mm and about 7 mm (e.g., about 3 mm, about 4 mm, about 5mm, about 6 mm, about 7 mm, ranges between such values, etc.). In someembodiments, the electrodes 203 have a surface area between about 0.5mm² and about 5 mm² (e.g., about 0.5 mm², about 1 mm², about 1.5 mm²,about 2 mm², about 2.5 mm², about 3 mm², about 3.5 mm², about 4 mm²,about 4.5 mm², about 5 mm², ranges between such values, etc.). Theelectrodes 203 are generally aligned longitudinally andcircumferentially, but offset electrodes 203 are also possible. Thecoverage of the right pulmonary artery 206 provided by the electrodearray 201 is longitudinally between about 25 mm and about 35 mm (e.g.,about 25 mm, about 28 mm, about 31 mm, about 35 mm, ranges between suchvalues, etc.) and is circumferentially between about 80° and about 120°(e.g., about 80°, about 90°, about 100°, about 110°, about 120°, rangesbetween such values, etc.). The electrode array 201 may cover, forexample, between about 25% and about 50% (e.g., about 25%, about 30%,about 35%, about 40%, about 45%, about 50%, ranges between such values,etc.) of the circumference of the vessel. In some embodiments, theelectrode array 201 comprises a 3×3 matrix, a 3×4 matrix, a 3×5 matrix,a 4×4 matrix, a 4×5 matrix, or a 5×5 matrix. Larger matrices may be morelikely to capture the target nerve by at least one combination ofelectrodes 203, and smaller matrices may be easier to deliver to thetarget site.

FIG. 2I is a schematic illustration of heart vasculature and surroundingnerves. Similar to FIGS. 2G and 2H, FIG. 2I shows a pulmonary trunk 202,a right pulmonary artery 206, and a left pulmonary artery 208. FIG. 2Ialso shows traces of the approximate crossing locations ofinterventricular sulcus nerves 215, 217 along the right pulmonary artery206 and the pulmonary trunk 202. Stimulation of one or both of thenerves 215, 217 may increase contractility, for example more than heartrate or without affecting heart rate. The electrode matrix 201,including electrodes 203 a, 203 b, 203 c, 203 d, 203 e, 203 f, etc., isshown in phantom in the approximate position of FIGS. 2G and 2H.

In some embodiments, particular electrodes can be selected to target orcapture one or more nerves. The electrodes 203 a, 203 b can be used totarget the nerve 215, for example, in a generally transverse manner. Theelectrodes 203 a, 203 c can be used to target the nerve 215, forexample, in a generally parallel manner. The electrodes 203 c, 203 d canbe used to target the nerve 215 as well as the nerve 217, for example,in a generally transverse manner. The electrodes 203 e, 203 f can beused to target the nerve 217, for example, in a generally mixedtransverse-parallel manner. In some embodiments, the two electrodes canbe used in a bipolar manner, with one of the two electrodes beingpositive and the other of the two electrodes being negative. In someembodiments, more than two electrodes can be used, with two or moreelectrodes being positive and two or more electrodes being negative.

As described in further detail herein, upon placement of the electrodearray, electrode combinations can be stimulated to test their effect.Some combinations may produce a better result but be more likely toresult in a side effect, some combinations may produce a better resultbut be less repeatable, some combinations may affect one nerve but notmultiple nerves, etc. In some embodiments, a plurality of electrodecombinations or independent outputs can be used in parallel or inseries. For example, the electrodes 203 a, 203 b can be used to targetthe nerve 215 for a first duration and the electrodes 203 e, 203 f canbe used to target the nerve 217 for a second duration. The secondduration may at least partially overlap the first duration, fullyoverlap the first duration (e.g., starting at the same time, ending atthe same time, starting after the first duration starts, ending beforethe first duration ends, and combinations thereof) or may be temporallyspaced from the first duration by a third duration. The third durationmay be zero (e.g., the second duration starting as the first durationends).

In a study of multiple cadavers, the mean diameter 206 d of the rightpulmonary artery 206 proximate to the branch point 207 was about 26.5 mmwith a standard deviation of about 4.6 mm. Assuming a circular vessel,the mean circumference of the right pulmonary artery 206 proximate tothe branch point 207 is about 83 mm. If the goal is 30% coverage of thecircumference, then an electrode matrix should have a circumferentiallength of about 25 mm (83 mm×30%). Other electrode matrix dimensions canbe estimated or calculated based on other dimensions (e.g., vesseldiameter at other points, measured vessel diameter, diameters of othervessels, vessel lengths, etc.), target coverage percentage, nervelocation variability, placement accuracy, stimulation parameters, etc.

FIG. 2J is a schematic illustration of vasculature and surroundingnerves. The superior vena cava 232, as discussed above, supplies bloodto the right atrium of the heart. The vessels supplying blood to thesuperior vena cava 232 include the right innominate vein or rightbrachiocephalic vein 253 and the left innominate vein or leftbrachiocephalic vein 255. The vessels supplying blood to the rightbrachiocephalic vein 253 include the right subclavian vein 257 and theright internal jugular vein 259. The vessels supplying blood to the leftbrachiocephalic vein 255 include the left subclavian vein 261 and theleft internal jugular vein 263. The inferior thyroid vein 265 alsosupplies blood to the superior vena cava 232. Although other nerves arepresent surrounding the vasculature illustrated in FIG. 2F, the rightvagus nerve 267 is illustrated as an example. The left vagus nerve runsclose to the left internal jugular vein 263 and the common carotidartery, and then crosses the left brachiocephalic vein 255. Thoracicsympathetic cardiac branches also cross the left brachiocephalic vein255 closer to the crown of the aorta and more medial, generally betweenthe junction of the left subclavian vein and the left internal jugularvein 263 and about half of the length of the left brachiocephalic vein253. Vasculature that may not typically be characterized ascardiovasculature may also be used in accordance with certain methodsand systems described herein.

FIG. 2K is another schematic illustration of a heart 200 and surroundingnerves. As described in detail herein, nerves affecting contractility(e.g., left ventricle contractility) may be targeted for neuromodulationby positioning a catheter in the pulmonary artery (e.g., right pulmonaryartery, pulmonary trunk, left pulmonary artery). In some embodiments, anerve such as the right stellate CPN 244 may also or alternatively betargeted by positioning a device at a location 272 in the leftsubclavian artery 274 and/or the location 276 in the descending aorta278. Positioning in the left common carotid artery 280 is also possible.In FIG. 2K, an example stimulation device 282 is shown at the locations272, 276. Other stimulation devices are also possible. In embodimentscomprising multiple stimulation devices, the stimulation devices may bethe same, different, or similar (as a non-limiting example, having asame structure but different dimensions).

FIG. 2L illustrates an example stimulation device 282. The stimulationdevice 282 may be used, for example, to target stimulation of a rightstellate CPN 244 or another nerve. The device 282 comprises a skeletalstructure 284, for example a stent, hoops, etc. The skeletal structure284 may comprise a shape memory material (e.g., nitinol) that isself-expanding. The device 282 further comprise a mesh or membrane 286attached to the skeletal structure 284. The mesh 286 may comprise, forexample, Dacron®. One side of the device 282 comprises an electrodearray 288. The electrode array 288 may have an area between about 0.5cm² and about 3 cm² (e.g., about 0.5 cm², about 1 cm², about 1.5 cm²,about 2 cm², about 2.5 cm², about 3 cm², ranges between such values,etc.). The electrode array 288 may be powered by implantable electronics290. The electronics 290 may include, for example, non-volatile memory(e.g., storing electrode combinations and parameters), ASIC stimulationengine and logic, RF engine, battery power, and a sensor (e.g., pressuresensor, contractility sensor, combinations thereof, etc.). The device282 may be positioned by a catheter routed through vasculature (e.g.,from a femoral or radial artery). The device 282 may be positionableuntil the target nerve is stimulated. In some embodiments, the electrodearray 288 may be electronically repositionable (e.g., as described withrespect to FIGS. 32A-32D). In some embodiments, an external device(e.g., worn by the subject) can power and/or control the device 282. Inembodiments in which the electronics 290 can power and/or control thedevice 282, the device 282 may be fully implantable. In certain suchembodiments, the device 282 may be combined with a pacemaker,defibrillator, or other implantable stimulation device.

FIG. 3A is a side perspective and partial cross-sectional view of anexample of a catheter 300. FIG. 3B is a distal end view of the catheter300 of FIG. 3A as viewed along line 3B-3B in FIG. 3A. The catheter 300includes an elongate body 302 having a first for proximal end 304 and asecond or distal end 306. The second end 306 is distal to the first end304. The elongate body 302 includes a longitudinal axis 308 that extendsthrough the first end 304 and the second end 306 of the elongate body302. A first plane 310 extends through the longitudinal axis 308 overthe length of the elongate body 302. As used herein, a plane is animaginary flat surface on which a straight line joining any two pointson it would wholly lie, and is used herein to help orientate therelative position of structures on the catheter 300. The first plane 310is used herein, among other reasons, to help explain the relativeposition of electrodes. The catheter 300 further includes at least twoelongate stimulation members 314 (as illustrated in FIGS. 3A and 3B, 314a and 314 b). The stimulation members 314 extend from the elongate body302. Each of the at least two elongate stimulation members 314 a, 314 bcurves into a first volume 316 defined at least in part by the firstplane 310. For example, the at least two elongate stimulation members314 extend from approximately the second end 306 of the elongate body302 into the first volume 316.

Each of the at least two elongate stimulation members 314 comprises atleast one electrode 318. The at least one electrode 318 on each of theelongate stimulation members 314 form an electrode array in the firstvolume 316 that is at least partially defined by the first plane 310.The at least one electrode 318 on each of the stimulation members 314are electrically isolated from one another. In some embodiments, thestimulation members 314 comprise an electrically insulating material.

Each of the at least one electrodes 318 is coupled to a correspondingconductive element 320. The conductive elements 320 are electricallyisolated from each other and extend through and/or along the stimulationmembers 314 from each respective electrode 318 through the first end 304of the elongate body 302. The conductive elements 320 terminate at aconnector port, where each of the conductive elements 320 can bereleasably coupled to a stimulation system, for example as discussedherein. In some embodiments, the conductive elements 320 are permanentlycoupled to the stimulation system (e.g., not releasably coupled). Thestimulation system can be used to provide stimulation electrical energythat is conducted through the conductive elements 320 and deliveredacross combinations of the electrodes 318 in the electrode array.

Each of the at least two elongate stimulation members 314 includes astimulation member elongate body 322 having a distal end 324. The distalend 324 of the stimulation member elongate body 322 for each of theelongate stimulation members 314 extends from the elongate body 302.Each of the elongate body 302 and the stimulation member elongate body322 include a surface defining a lumen 328 through which a wire 326 mayextend. The wire 326 is joined to its respective stimulation memberelongate body 322 at or near the distal end 324 of the stimulationmember elongate body 322, where the wire 326 then freely extends throughthe lumen 328 in the elongate stimulation member 314 past the first end304 of the elongate body 302. The lumen 328 is dimensioned to allow thewire 326 to be moved longitudinally within the lumen 328. The portion ofthe wire 326 extending from the first end 304 can be used to applypressure against the stimulation member elongate body 322 at or near thedistal end 324 of the stimulation member elongate body 322, where thewire 326 under such pressure can deflect or bend, which can impart acurve into each of the at least two elongate stimulation members 314into the first volume 316 defined at least in part by the first plane310. The at least two elongate stimulation members 314 extend radiallyaway from the elongate body 302 over a range of distances depending uponhow much pressure is applied to the wires 326. The curves of the atleast two elongate stimulation members 314 can have a radius ofcurvature that changes along the length of the stimulation memberelongate body 322 (e.g., as illustrated in FIG. 3A).

In some embodiments, the at least two elongate stimulation members 314only curve in the first volume 316 defined at least in part by the firstplane 310. A second volume 330 opposite the first volume and defined atleast in part by the first plane 310 may contain no electrodes. In someembodiments, the at least two elongate stimulation members 314 include afirst elongate stimulation member 314 a and a second elongatestimulation member 314 b. A second plane 312 perpendicularly intersectsthe first plane 310 along the longitudinal axis 308 of the elongate body302. The first plane 310 and the second plane 312 divide the firstvolume 316 into a first quadrant volume 332 and a second quadrant volume334. In some embodiments (e.g., as illustrated in FIGS. 3A and 3B), thefirst elongate stimulation member 314 a curves into the first quadrantvolume 332 and the second elongate stimulation member 314 b curves intothe second quadrant volume 334.

The catheter 300 may include an anchor member 336 that extends from theelongate body 302 into the second volume 330. The anchor member 336 maynot include or be devoid of an electrode. The anchor member 336 is notocclusive within vasculature and/or does not encourage thrombosis orcoagulation of blood within vasculature. The anchor member 336 and theelongate body 302 include surfaces defining a lumen 338 through whichwire 340 can pass. The wire 340 is joined to the anchor member 336 at ornear a distal end 342 of the member 336, where the wire 340 freelyextends through the lumen 338 of the anchor member 336 past the firstend 304 of the elongate body 302. The lumen 338 is dimensioned to allowthe wire 340 to be moved longitudinally within the lumen 338. Theportion of the wire 340 extending from the first end 304 can be used toapply pressure against the anchor member 336 at or near its distal end342, where the wire 340 under such pressure can deflect or bend, whichcan impart a curve into the anchor member 336. The anchor member 336 canextend radially away from the elongate body 302 over a range ofdistances depending upon how much pressure is applied to the wire 340.The anchor member 336 can be used to bring the electrodes 318 intocontact with a vascular luminal surface (e.g., a posterior surface ofthe main pulmonary artery and/or one or both of the pulmonary arteries),for example as described herein, by application of a variety ofpressures. Optionally, the anchor member 336 can be configured toinclude one or more electrodes.

Each of the wires 326 and the wire 340, upon being used to impart thecurves in their respective members, can then be releasably locked inplace by inhibiting or preventing longitudinal movement of the wire 326,340 relative the elongate body 302. For example, a clamp or other devicecan be used to create contact between the wire 326, 340 and the surfaceof the lumen 328, 338 sufficient to inhibit or prevent the wire 326, 340from moving relative the surface of the lumen 328, 338. This clampingaction can also function as a hemostasis valve to reduce or minimizeblood loss.

FIGS. 3A and 3B also illustrate a pulmonary artery catheter 344(partially shown to show detail of catheter 300) that can be used withthe catheter 300 in a catheter system. The pulmonary artery catheter 344includes an elongate catheter body 346 having a first or proximal end348, a second or distal end 350, a peripheral surface 352, and aninterior surface 354 opposite the peripheral surface 352. The interiorsurface 354 at least partially defines a lumen 356 that extends betweenthe first end 348 and the second end 350 of the elongate catheter body346. The lumen 356 is of a sufficient size and shape to house at least aportion of the catheter 300 inside the lumen 356 during delivery of thecatheter 300. For example, the anchor member 336 and the at least twoelongate stimulation members 314, along with a least a portion of theelongate body 302, can be positioned at least partially n the lumen 356.The anchor member 336, the at least two elongate stimulation members314, and at least a portion of the elongate body 302 can be deployedfrom the distal end 350 of the pulmonary artery catheter 344 during thedelivery and implantation of the catheter 300.

The pulmonary artery catheter 344 can further include an inflatableballoon 358 on the peripheral surface 352 of the elongate catheter body346. The inflatable balloon 358 includes a balloon wall 360 having aninterior surface 362 that, along with a portion of the peripheralsurface 352 of the elongate catheter body 346, at least partiallydefines a fluid-tight volume 364. The pulmonary artery catheter 344further includes an inflation lumen 366 that extends through theelongate catheter body 346. The inflation lumen 366 includes a firstopening 368 into the fluid-tight volume 364 of the inflatable balloon358 and a second opening 370 proximal to the first opening 368 to allowfor a fluid to move in and out of the fluid tight volume 364 to inflateand deflate the balloon 358, respectively. A syringe or other suchdevices containing the fluid (e.g., saline, contrast, gas (e.g.,oxygen)) can be used to inflate and deflate the balloon 358. FIG. 3Ashows the balloon 358 in an inflated state, while FIG. 3B shows theballoon 358 in a deflated state.

The catheter system can be used to position the catheter 300 in the mainpulmonary artery and/or one or both of the pulmonary arteries of thepatient, for example as described herein. The pulmonary artery catheter344, with the catheter 300 positioned within the lumen 356, can beintroduced into the vasculature through a percutaneous incision andguided to the right ventricle. For example, the catheter 300 can beinserted into the vasculature via a peripheral vein of the arm (e.g., aswith a peripherally inserted central catheter). Changes in a subject'selectrocardiography and/or pressure signals from the vasculature can beused to guide and locate the catheter 300 within the subject's heart.Once in the proper location, the balloon 358 can be inflated to allowthe pulmonary artery catheter 344 and the catheter 300 to be carried bythe flow of blood from the right ventricle to the main pulmonary arteryand/or one of the pulmonary arteries. Optionally, various imagingmodalities can be used in positioning the catheter 300 and/or cathetersystem in the main pulmonary artery and/or one of the pulmonaryarteries. Such imaging modalities include, but are not limited to,fluoroscopy, ultrasound, electromagnetic, and electropotentialmodalities.

The catheter system can be advance along the main pulmonary artery untilthe distal end 350 of the pulmonary artery catheter 344 contacts the topof the main pulmonary artery (e.g., a location distal to the pulmonaryvalve and adjacent to both of the pulmonary arteries). The advancementcan be with the balloon 358 in the inflated or deflated state. Once thedistal end 350 of the pulmonary artery catheter 344 reaches the top ofthe main pulmonary artery, the elongate catheter body 346 can be movedrelative the catheter 300 so as to deploy the catheter 300 from thelumen 356 of the pulmonary artery catheter 344.

The peripheral surface of the catheter body 302 may include markings,for example starting and extending from the first end 304 towards thesecond end 306 of the catheter 300. The distance between the markingscan be of units (e.g., millimeters, inches, etc.), which can allow thelength between the distal end 350 of the pulmonary artery catheter 344and the top of the main pulmonary artery to be determined. A marking canalso or alternatively be provided on the peripheral surface of thecatheter body 302 that indicates when the distal end 350 of thepulmonary artery catheter 344 is clear of the anchor member 336 and theelongate stimulation members 314. In some embodiments, a positioninggauge can be used to locate the catheter 300 within the main pulmonaryartery, for example as discussed in further detail herein.

The ability to measure distance from the top of the main pulmonaryartery may be helpful in placing the electrodes 318 in a desiredlocation in the main pulmonary artery. In addition or alternative tomeasuring the distance from which the second end 306 of the elongatebody 302 is placed from the top of the main pulmonary artery, theelongate body 302 can also be used to identify or map a position (e.g.,a desired or optimal position) for the electrodes 314 within thevasculature. For example, the second end 306 of the elongate body 302can be positioned at a desired distance from the top of the mainpulmonary artery using the markings on the peripheral surface of thecatheter body 302. The wires 326 and 340 can then be used to impart thecurves into the elongate stimulation members 314 and the anchor member336. Using the wires 326 and the wire 340, the elongate stimulationmembers 314 and the anchor member 336 can be imparted with curves ofsufficient size to contact a surface of the main pulmonary artery, suchas the anterior surface of the main pulmonary artery, which can bringthe electrodes 318 into contact with the main pulmonary artery or one ofthe pulmonary arteries (the left pulmonary artery or the right pulmonaryartery). The anchor member 336, as will be appreciated, biases and helpsto anchor the electrodes 318 along the vessel surface (e.g., along theposterior surface of the main pulmonary artery or one of the pulmonaryarteries (the left pulmonary artery or the right pulmonary artery)).

Due to its adjustable nature (e.g., depending at least partially on howmuch pressure or longitudinal force is applied to the wire 340), theanchor member 336 can be used to bring the electrodes 318 into contactwith the luminal surface of the main pulmonary artery or one of thepulmonary arteries with a variety of pressures. For example, the anchormember 336 can bring the electrodes 318 into contact with the luminalsurface of the main pulmonary artery or one of the pulmonary arterieswith a first pressure. Using the stimulation system, for example asdiscussed herein, stimulation electrical energy can be delivered acrosscombinations of two or more of the at least one electrode 318 in theelectrode array. It is possible for the subject's cardiac response tothe stimulation electrical energy to be monitored and recorded forcomparison to other subsequent tests.

For any of the catheters and/or catheter systems discussed herein, anycombination of electrodes, including reference electrodes (e.g., asdiscussed herein), positioned n or on the subject's body, can be used inproviding stimulation to and sensing cardiac signals from the subject.

The pressure may be reduced and the elongate body 302 can be rotated ineither a clockwise or counter-clockwise direction to reposition theelectrodes 318 in contact with the luminal surface of the main pulmonaryartery or one of the pulmonary arteries. The stimulation system can beused to deliver stimulation electrical energy across combinations of twoor more of the at least one electrode 318 in the electrode array. Thesubject's cardiac response to this test can then be monitored andrecorded for comparison to previous and/or subsequent tests. In thisway, a preferred location for the position of the electrodes 318 alongthe luminal surface of the main pulmonary artery or one of the pulmonaryarteries can be identified. Once the preferred location for the positionof the electrodes 318 has been identified, the wire 340 can be used toincrease the pressure applied by the anchor member 336, which can helpto further anchor the catheter 300 in the patient.

FIG. 4A is a side perspective and partial cross-sectional view ofanother example of a catheter 400. FIG. 4B is a distal end view of thecatheter 400 of FIG. 4A as viewed along line 4B-4B in FIG. 4A. Thecatheter 400 includes at least the structures as discussed herein withrespect to the catheter 300, so a detailed discussion of shared orsimilar elements is not repeated but the element numbers are incrementedin the hundreds place in FIGS. 4A and 4B with the understanding that thediscussion of these elements is implicit.

Each of the at least two elongate stimulation members 414 comprises aplurality of electrodes 418 (e.g., three electrodes 418 as illustratedin FIGS. 4A and 4B, although other numbers (e.g., one, two, four, five,or more) are also possible). The electrodes 418 on the elongatestimulation members 414 form an electrode array. The electrodes 418 oneach of the stimulation members 414 are electrically isolated from oneanother.

The catheter 400 further includes a structure 472 extending between atleast two of the least two elongate stimulation members 414. Thestructure 472 is flexible such that it can transition between a deliveryor low-profile state (radially folded state) that allows the structure472 to be delivered into the main pulmonary artery and/or one of thepulmonary arteries, and a deployed or expanded state (radially expanded)as illustrated in FIG. 4A. The wires 426 and the least two elongatestimulation members 414 can be used to bring the structure 472 into itsdeployed or expanded state, for example as described herein. An exampleof the structure 472 is a mesh structure.

The structure 472 comprises a plurality of flexible strands that areconnected to form a pattern of openings between the strands. One or moreelectrodes 474 can be present at one or more of the connections of thestrands. The electrodes 474 can themselves form an electrode array, ortogether with the electrodes 418 may form an electrode array. Inembodiments comprising a plurality of electrodes 474, the electrodes 474can be aligned (e.g., as illustrated in FIG. 4A), in a two-dimensionalpattern, in a three-dimensional pattern (e.g., accounting for thecurvature of the stimulation member elongate body 422), or scatteredwithout a specific order. The strands can comprise the same material asthe elongate body 402 and/or the elongate stimulation members 414 ormaterial that is different than the elongate body 402 and/or theelongate stimulation members 414. The strands may comprise insulativematerial. Examples of insulative material for one or more portions ofthe catheters and structures provided herein can include, but are notlimited to, medical grade polyurethanes, such as polyester-basedpolyurethanes, polyether-based polyurethanes, and polycarbonate-basedpolyurethanes; polyamides, polyamide block copolymers, polyolefins suchas polyethylene (e.g., high-density polyethylene, low-densitypolyethylene), and polyimides, among others.

The structure 472 can have a predefined shape that helps to locate andposition at least one of the elongate stimulation members 414 and theelectrodes 418 thereon. For example, the structure 472 can be used toadjust and/or maintain the distance between electrodes 418 on theadjacent stimulation members 414.

The structure 472 can include one or more additional electrode 474. Theadditional electrode 474 can either be positioned on the structure 472or formed as an integral part of the structure 472. Each of theadditional electrodes 474 may be electrically isolated from each of theother electrodes 474 and/or the electrodes 418. The additionalelectrodes 474 each include a conductive element 476. Each of theconductive elements 476 is electrically isolated from each other and canextend through the strands of the structure 472 from each respectiveadditional electrode 474, through the stimulation members 414 and theelongate body 402, to the first end 404. The conductive elements 476terminate at a connector port, where each of the conductive elements 420and 476 can be releasably coupled to the stimulation system, for exampleas discussed herein. In some embodiments, the conductive elements 420may be non-releasably or permanently coupled to the stimulation system.The stimulation system can be used to provide stimulation electricalenergy that is conducted through the conductive elements 420, 476 tocombinations of at least one of the additional electrodes 474 and/or atleast one of the electrodes 418.

FIG. 4C is a side perspective view of an example of a portion 401 of acatheter. The portion 401 may be used with the catheter 300, 400, othercatheters described herein, and the like. The portion 401 comprises aplurality of elongate splines 471. The splines 471 may compriseresilient or shape memory material configured to form an expanded shape(e.g., the conical shape shown in FIG. 4C or another shape) when notconfined, for example in a catheter body. The portion 401 comprises astructure 472 extending between at least two of the elongate splines471. One or more electrodes 474 can be coupled to the structure 472(e.g., by adhering, soldering, welding, tying, combinations thereof, andthe like). The electrodes 474 may be aligned with the splines 471,between the splines 471, and combinations thereof. For example, in theportion 401, the structure 472 is over three circumferentially-offsetsplines 471. The middle set of four electrodes 474 is aligned with amiddle spline 471 and the outer sets of four electrodes 474 are betweenthe middle spline 471 and the outer splines 471, forming a 3×4 array ormatrix of electrodes 474.

In embodiments comprising a plurality of electrodes 474, the electrodes474 can be aligned (e.g., as illustrated in FIG. 4C) in atwo-dimensional pattern, in a three-dimensional pattern (e.g.,accounting for the curvature of the expanded shape of the splines 471),or scattered without a specific order. The electrodes 474 can themselvesform an electrode array, or together with other electrodes (e.g., on thesplines 471) may form an electrode array.

The structure 472 can comprise a woven or knitted mesh or membrane. Thestructure may comprise insulative material, for example medical gradepolyurethanes, such as polyester-based polyurethanes, polyether-basedpolyurethanes, and polycarbonate-based polyurethanes; polyamides,polyamide block copolymers, polyolefins such as polyethylene (e.g.,high-density polyethylene, low-density polyethylene), and polyimides,and the like.

In some embodiments, the structure 472 may be slid over the splines 471.For example, lateral edges or medial sections of the structure 472 mayinclude loops configured to be slid over the splines 471. Althoughillustrated in FIG. 4C as arcuate over part of the circumference of theportion 401, the structure 472 may be arcuate around an entirecircumference of the portion 401. In certain such embodiments, thestructure 472 can be slid over the splines 471 as a telescoping tube.The structure 472 may be coupled to the splines 471 and/or tethered to acatheter.

In some embodiments, a plurality of structures 472 may be used. Forexample, a plurality of partially arcuate structures may be positionedaround the splines 471 (e.g., in different circumferential positions, inoverlapping circumferential positions, and/or in the samecircumferential position (e.g., with different electrode 474 patterns)).For another example, a structure 472 may be substantially tubular suchthat it can be slid over a single spline, and a plurality of suchstructures 472 can be used on different splines or even the same spline.

Forming electrodes on a structure 472 can aid in manufacturing. Forexample, the electrodes 474 can be coupled to the structure 472independent of forming the splines 471 (e.g., as opposed to formingelectrodes in or on the splines 471). In some embodiments, theelectrodes 474 can be formed on the structure 472, for example like flexcircuit manufacturing. The structure 472 may also help to positionconductive elements electrically connecting the electrodes 474 to astimulation system.

The catheter 400 optionally comprises an anchor wire 478 extendinglongitudinally through the stimulation member elongate body 422. Theelongate body 402 and the member elongate body 422 include a surface atleast partially defining a lumen having a first opening at the proximalend 404 and a second opening at or adjacent to the distal end 424 of thestimulation member elongate body 422. The anchor wire 478 freely passesthrough the lumen, with a first end 480 extending from the elongate body422 at the proximal end 404 of the elongate body 402 and a second end482 comprising an anchoring structure (e.g., a barb) that extends fromthe second opening at or adjacent to the distal end 424 of thestimulation member elongate body 422. The anchor wire 478 can be advancethrough the lumen (e.g., longitudinal force can be applied to the firstend 480 of the anchor wire 478) to extend the anchoring structure awayfrom the stimulation member elongate body 414. The anchor member 436 mayhelp to anchor the catheter 400 in the subject, for example as discussedherein. The anchor wire 478 can also or alternatively be used to helpsecure the catheter 400 in the subject at a desired location. One ormore of the anchor wire 478 and the associated structures can also beincluded with the catheter 300. Optionally, the anchor wire 478 can beconfigured and used as an electrode with the stimulation system of thepresent disclosure. For example, the anchor wire 478 can be configuredas an anode and one or more of the electrodes 418, 474 can be configuredas a cathode and/or an anode, and/or the anchor wire 478 can beconfigured as a cathode and one or more of the electrodes 418, 474 canbe configured as an anode and/or a cathode.

FIG. 4A also illustrates a pulmonary artery catheter 444 (partiallyshown to show detail of catheter 400), for example similar to thepulmonary artery catheter 344 discussed herein. A catheter systemcomprising the pulmonary artery catheter 444 can be used to position thecatheter 400 in the main pulmonary artery and/or one of the pulmonaryarteries of the patient, for example as described herein. The pulmonaryartery catheter 444 with the catheter 400 positioned within the lumen454 is introduced into vasculature through a percutaneous incision andguided to the right ventricle. The balloon 458 is inflated through theinflation lumen 466, allowing the pulmonary artery catheter 444 and thecatheter 400 to be carried by the flow of blood from the right ventricleto the main pulmonary artery or one of the pulmonary arteries.

The catheter system shown in FIGS. 4A and 4B comprises an optionalpositioning gauge 484. The positioning gauge 484 includes an elongategauge body 486 having a first end 488 and a bumper end 490 distal to thefirst end 488. The elongate gauge body 486 can be moved longitudinallywithin a lumen 492 at least partially defined by a surface that extendsthrough the elongate body 402 from its first end 404 through the secondend 406. The bumper end 490 can have a shape with an example surfacearea being no less than a surface area of the distal end 406 of theelongate body 402 taken perpendicularly to the longitudinal axis 408.The elongate gauge body 486 extends through the lumen 492 to positionthe bumper end 490 distal to the second end 406 of the elongate body402. The first end 488 of the position gauge 484 extends proximally fromthe first end 404 of the elongate body 402. The elongate gauge body 486may include a marking 494 that indicates a length between the second end406 of the elongate body 402 and the bumper end 490 of the positiongauge 484.

During navigating the catheter 400, the bumper end 490 of thepositioning gauge 484 may be approximately longitudinally even with thedistal end 424 of the stimulation member elongate body 422, the distalend 442 of the anchor member 436, and the distal end 450 of thepulmonary artery catheter 444 (e.g., the elongate body 402, the anchormember 436, and the elongate stimulation members 414 are positioned inthe lumen 456 of the pulmonary artery catheter 444). In thisconfiguration, the catheter system can be advance along the mainpulmonary artery until the bumper end 490 of the positioning gauge 484contacts the top of the main pulmonary artery (e.g., a location distalto the pulmonary valve and adjacent to both the pulmonary arteries). Thecatheter system can be distally advanced when beyond the pulmonary valvewith the balloon 458 in the inflated or deflated state.

Once the bumper end 490 contacts the top of the main pulmonary artery,the pulmonary artery catheter 444 (with the catheter 400 positioned inthe lumen 456) can be moved relative the bumper end 490 (e.g., thepulmonary artery catheter 444 and the catheter 400 can be moved awayfrom the bumper end 490). As the pulmonary artery catheter 444 and thecatheter 400 move relative to the bumper end 490, the markings 494 onthe elongate gauge body 486 can be used to indicate a length between thedistal end 224 of the stimulation member elongate body 422, the distalend 442 of the anchor member 436, the distal end 450 of the pulmonaryartery catheter 444, and the bumper end 490 of the position gauge 484.

The distance between the markings 494 can be in certain units (e.g.,millimeters, inches, etc.), which can allow the length the between thedistal end 424 of the stimulation member elongate body 422, the distalend 442 of the anchor member 436, and the distal end 450 of thepulmonary artery catheter 444 to be determined. Once a length that isdesired is achieved, the pulmonary artery catheter 444 can be movedrelative the catheter 400 so as to deploy the anchor member 436 and theelongate stimulation members 414 with the electrodes 418 within the mainpulmonary artery or one of the pulmonary arteries.

The ability to measure distance from the top of the main pulmonaryartery may be helpful in placing the electrodes 418 in a desiredlocation in the main pulmonary artery or one of the pulmonary arteries.For example, the distal end 424 of the stimulation member elongate body422 and the distal end 442 of the anchor member 436 can be positioned atthe desired distance from the top of the main pulmonary artery using themarkings 494 on the peripheral surface of the positioning gauge 484. Thewires 426, 440 can be used to impart curves into the elongatestimulation members 414 and the anchor member 436, respectively. Usingthe wires 426 and the wire 440, the elongate stimulation members 414 andthe anchor member 436 can be provided with curves of sufficient size tocontact the anterior surface of the main pulmonary artery and bring theelectrodes 418 into contact with the luminal surface of the mainpulmonary artery. The anchor member 436 can bias and help to anchor theelectrodes 418 along the vessel surface (e.g., along the posteriorsurface of the main pulmonary artery). Optionally, the anchor member 436can be configured to include one or more electrodes 418, for example asdiscussed herein.

Due to its adjustable nature (e.g., changing apposition pressuredepending on the amount of longitudinal force or pressure is applied tothe wire 440), the anchor member 436 can be used to bring the electrodes418 into contact with the luminal surface of the main pulmonary arteryor one of the pulmonary arteries under a variety of pressures. Forexample, the anchor member 436 can bring the electrodes 418 into contactwith the luminal surface of the main pulmonary artery or one of thepulmonary arteries under a first pressure. Using stimulation electricalenergy from the stimulation system, electrical energy can be deliveredacross combinations of two or more of the electrodes 418, 474. Thesubject's cardiac response to the stimulation electrical energy can thenbe monitored and recorded for comparison to subsequent tests. Ifdesired, the longitudinal pressure applied to the anchor member 436 canbe reduced, and the elongate body 402 can be rotated in either aclockwise or counter-clockwise direction and/or lengthwise relative tothe top of the main pulmonary artery or one of the pulmonary arteries toreposition the electrodes 418 in contact with the luminal surface of themain pulmonary artery or one of the pulmonary arteries. The stimulationsystem can again be used to deliver stimulation electrical energy acrosscombinations of two or more of the electrodes 418, 474. The subject'scardiac response to this subsequent test can then be monitored andrecorded for comparison to previous and subsequent tests. In this way, apreferred location for the position of the electrodes 418 along theluminal surface of the main pulmonary artery or one of the pulmonaryarteries can be identified. Once identified, the wire 440 can be used toincrease the pressure applied by the anchor member 436, thereby helpingto better anchor the catheter 400 in the patient.

Referring now to FIG. 5 , an embodiment of a catheter 500 is shown,where the catheter 500 may include the structures and features of theother catheters discussed herein. As illustrated, the catheter 500includes an elongate body 502 having a first end 504 and a second end506 distal from the first end 504. As illustrated, the elongate body 502includes an elongate radial axis 508 that extends through the first end504 and the second end 506 of the elongate body 502. As illustrated, afirst plane 510 extends through the elongate radial axis 508 over thelength of the elongate body 502. A second plane 512 perpendicularlyintersects the first plane 510 along the longitudinal axis 508 of theelongate body 502. The first plane 510 and the second plane 512 divide afirst volume 516 into a first quadrant volume 532 and a second quadrantvolume 534. The catheter 500 further includes at least two elongatestimulation members 514, as discussed herein, that extend from theelongate body 502. Each of the at least two elongate stimulation members514-1 and 514-2 curves into a first volume 516 defined at least in partby the first plane 510. For example, the at least two elongatestimulation members 514 may extend from approximately the second end 506of the elongate body 502 into the first volume 516.

FIG. 5 also illustrates at least one electrode 518 on each of the atleast two elongate stimulation members 514. The at least one electrode518 on each of the elongate stimulation members 514 form an electrodearray in the first volume 516. The at least one electrode 518 on each ofthe elongate stimulation members 514 may be electrically isolated fromone another and/or may comprise an electrically insulating material. Thecatheter 500 also includes conductive elements 520 that extend throughand/or along each of the elongate stimulation members 514. As discussedherein, the conductive elements 520 can conduct electrical current tocombinations of two or more of the electrodes 518. The conductiveelements 520 may be electrically isolated from each other. Theconductive elements 520 may terminate at a connector port, where each ofthe conductive elements 520 can be releasably coupled to a stimulationsystem, for example as discussed herein. In some embodiments, theconductive elements 520 are permanently coupled to the stimulationsystem (e.g., not releasably coupled). The stimulation system can beused to provide stimulation electrical energy that is conducted throughthe conductive elements 520 and delivered across combinations of theelectrodes 518 in the electrode array.

Each of the at least two elongate stimulation members 514 includes astimulation member elongate body 522 having a distal end 524 that canmove relative to each other. In other words, the distal ends 524 of eachof the stimulation member elongate bodies 522 are free of each other. Asillustrated in FIG. 5 , the at least two elongate stimulation members514 curve only in the first volume 516 defined at least in part by thefirst plane 510. FIG. 5 also illustrates a second volume 530 defined atleast in part by the first plane 510 (being opposite the first volume516) that contains no electrodes. FIG. 5 also illustrates an embodimentin which the at least two elongate stimulation members 514 include afirst elongate stimulation member 514-1 and a second elongatestimulation member 514-2, where the first elongate stimulation member514-1 curves into the first quadrant volume 532 and the second elongatestimulation member 514-2 curves into the second quadrant volume 534, aspreviously discussed herein. The catheter 500 also includes an anchormember 536 that extends from the elongate body 502 into the secondvolume 530. As illustrated, the anchor member 536 does not include anelectrode. The anchor member 536 includes an elongate body 538 aspreviously discussed in connection with previous figures. Optionally,the anchor member 536 can be configured to include one or more of theelectrodes 518 as discussed herein.

Each of the at least two elongate stimulation members 514 and the anchormember 536 can also include a wire 566 extending longitudinally throughthe stimulation member elongate body 522 and the elongate body 538,respectively. The wire 566 can provide each of the at least two elongatestimulation members 514 and the anchor member 536 with a predefinedshape. For example, the wire 566 in each of the at least two elongatestimulation members 514 and the anchor member 536 can have a coil orhelical configuration that imparts a curve to the stimulation memberelongate body 522 and the elongate body 538, respectively. The wire 566can also impart stiffness to the stimulation member elongate body 522that is sufficient to maintain the predefined shape under the conditionswithin the vasculature of the patient. So, for example, the wire 566provides sufficient stiffness and flexibility to the stimulation memberelongate body 522 to elastically return the least two elongatestimulation members 514 to their curved configuration when placed in thevasculature of a patient.

The wire 566 can be formed of a variety of metals or metal alloys.Examples of such metals or metal alloys include surgical grade stainlesssteel, such as austenitic 516 stainless among others, and the nickel andtitanium alloy known as Nitinol. Other metals and/or metal alloys canalso be used as desired and/or required. The predefined shape may beadapted to conform to a particular anatomical structure (e.g., the rightor left pulmonary artery or other portion of a pulmonary trunk).

The at least two elongate stimulation members 514 can also include ananchor wire 544, as discussed herein, extending longitudinally through alumen in the stimulation member elongate body 522 and the elongate body502. The anchor wire 544 includes a first end 546 extending from theelongate body 502 and a second end 548 having an anchoring structure(e.g., a barb). The anchor wire 544 can be advanced through the lumen(e.g, longitudinal force can be applied to the first end 546 of theanchor wire 544) to extend the anchoring structure away from thestimulation member elongate body 514. In addition to the use of theanchor member 536 in helping to better anchor the catheter 500 in thepatient, as discussed herein, the anchor wire 544 can also be used tohelp secure the catheter 500 in the patient at the desired location.Optionally, the anchor wire 544 can be configured and used as anelectrode with the stimulation system of the present disclosure.

In accordance with several embodiments, the catheter 500 furtherincludes a pulmonary artery catheter 591, as discussed herein. Asillustrated, the pulmonary artery catheter 591 (partially shown to showdetail of catheter 500) that can be used with catheter 500 to providefor a catheter system. The pulmonary artery catheter 591 includes anelongate catheter body 5100 with a first end 5102, a second end 5104, aperipheral surface 5106 and an interior surface 5108, opposite theperipheral surface 5106. The interior surface 5108 defines a lumen 5110that extends between the first end 5102 and the second end 5104 of theelongate catheter body 5100. The lumen 5110 is of a sufficient size andshape to house at least a portion of the catheter 500 inside the lumen5110 during delivery of the catheter 500. For example, the anchor member536 and the at least two elongate stimulation members 514, along with aleast a portion of the elongate body 502, can be positioned within thelumen 5110 during delivery. The anchor member 536, the at least twoelongate stimulation members 514 and at least a portion of the elongatebody 502 can be deployed from the distal end 5104 of the pulmonaryartery catheter 591 during the delivery and implantation of the catheter500.

The pulmonary artery catheter 591 can further include an inflatableballoon 5112 on the peripheral surface 5106 of the elongate catheterbody 5100. The inflatable balloon 5112 includes a balloon wall 5114 withan interior surface 5116 that, along with a portion of the peripheralsurface 5106 of the elongate catheter body 5100, defines a fluid tightvolume 5118. The pulmonary artery catheter 591 further includes aninflation lumen 5120 that extends through the elongate catheter body5100, where the inflation lumen 5120 has a first opening 5122 into thefluid tight volume 5118 of the inflatable balloon 5112 and a secondopening 5124 proximal to the first opening 5122 to allow for a fluid tomove in the fluid tight volume 5118 to inflate and deflate the balloon5112, as discussed herein. The catheter system shown in FIG. 5 can beused, for example, to position the catheter 500 in the main pulmonaryartery 202 and/or one or both of the pulmonary arteries 206, 208 of thepatient, for example as described herein. The at least two elongatestimulation members 514 and the anchor member 536 can be repositionedwithin the lumen 5110 of the pulmonary artery catheter 591 by moving theelongate catheter body 5100 relative to the elongate body 502 back overthe at least two elongate stimulation members 514 and the anchor member536. The catheter system illustrated in FIG. 5 can optionally includethe positioning gauge, as discussed in connection with FIGS. 4A and 4B,for example.

Referring now to FIG. 6 , another embodiment of a catheter 600 is shown.As illustrated, the catheter 600 includes an elongate body 602 having afirst end 604 and a second end 606 distal from the first end 604. Asillustrated, the elongate body 602 includes an elongate radial axis 608that extends through the first end 604 and the second end 606 of theelongate body 602. As illustrated, a first plane 610 extends through theelongate radial axis 608 over the length of the elongate body 602. Asecond plane 612 perpendicularly intersects the first plane 610 alongthe longitudinal axis 608 of the elongate body 602. The first plane 610and the second plane 612 divide a first volume 616 into a first quadrantvolume 632 and a second quadrant volume 634. The catheter 600 includesat least two elongate stimulation members 614 that extend from theelongate body 602. Each of the at least two elongate stimulation members614-1 and 614-2 curves into a first volume 616 defined at least in partby the first plane 610. For example, the at least two elongatestimulation members 614 extend from approximately the second end 606 ofthe elongate body 602 into the first volume 616.

FIG. 6 also illustrates at least one electrode 618 on each of the atleast two elongate stimulation members 614. Multiple electrodes 618 onthe elongate stimulation members 614 may form an electrode array in thefirst volume 616. The catheter 600 also includes conductive elements 620that extend through and/or along each of the elongate stimulationmembers 614. As discussed previously, the conductive elements 620 canconduct electrical current to combinations of two or more of theelectrodes 618.

Each of the at least two elongate stimulation members 614 includes astimulation member elongate body 622 each having a distal end 624 thatextends from the elongate body 602. In some embodiments (such asillustrated in FIG. 6 ), the at least two elongate stimulation members614 curve only in the first volume 616 defined at least in part by thefirst plane 610. FIG. 6 also illustrates a second volume 630 defined atleast in part by the first plane 610 (being opposite the first volume616) that contains no electrodes. FIG. 6 further illustrates anembodiment in which the at least two elongate stimulation members 614include a first elongate stimulation member 614-1 and a second elongatestimulation member 614-2, where the first elongate stimulation member614-1 curves into the first quadrant volume 632 and the second elongatestimulation member 614-2 curves into the second quadrant volume 634,such as previously discussed herein. The catheter 600 also includes ananchor member 636 that extends from the elongate body 602 into thesecond volume 630. As illustrated, the anchor member 636 does notinclude an electrode. The anchor member 636 includes an elongate body638 such as previously discussed. Optionally, the anchor member 636 canbe configured to include one or more of the electrodes 618.

Each of the at least two elongate stimulation members 614 and the anchormember 636 can also include a wire 666 extending longitudinally throughand/or along the stimulation member elongate body 622 and the elongatebody 638, respectively. The wire 666 can provide each of the at leasttwo elongate stimulation members 614 and the anchor member 636 with apredefined shape. For example, the wire 666 in each of the at least twoelongate stimulation members 614 and the anchor member 636 can have acoil or helical configuration that imparts a curve to the stimulationmember elongate body 622 and the elongate body 638, respectively. Thewire 666 can also impart stiffness to the stimulation member elongatebody 622 that is sufficient to maintain the predefined shape under theconditions within the vasculature of the patient. So, for example, thewire 666 can provide sufficient stiffness and flexibility to thestimulation member elongate body 622 to elastically return the least twoelongate stimulation members 614 to their curved configuration whenplaced in the vasculature of a patient. The wire 666 can be formed of avariety of metals or metal alloys such as those as discussed herein inconnection with other embodiments.

The at least two elongate stimulation members 614 can also include ananchor wire 644 extending longitudinally through and/or along thestimulation member elongate body 622. The anchor wire 644 includes afirst end 646 extending from the elongate body 602 and a second end 648having an anchoring structure (e.g., a barb). Longitudinal force appliedto the first end 646 of the anchor wire 644 advances the anchor wire 644through the stimulation member elongate body 614 to extend the anchoringstructure away from the stimulation member elongate body 614.Optionally, the anchor wire 644 can be configured and used as anelectrode with the stimulation system of the present disclosure.

The catheter 600 further includes a pulmonary artery catheter 691, aspreviously discussed herein. As illustrated, the pulmonary arterycatheter 691 (partially shown to show detail of catheter 600) can beused with the catheter 600 to provide a catheter system. The pulmonaryartery catheter 691 includes an elongate catheter body 670 with a firstend 680, a second end 682, a peripheral surface 676 and an interiorsurface 672, opposite the peripheral surface 676. The interior surface672 defines a lumen 674 that extends between the first end 680 and thesecond end 682 of the elongate catheter body 670. The lumen 674 may beof a sufficient size and shape to house at least a portion of thecatheter 600 inside the lumen 674 during delivery of the catheter 600.For example, the anchor member 636 and the at least two elongatestimulation members 614, along with a least a portion of the elongatebody 602, can be positioned within the lumen 674. The anchor member 636,the at least two elongate stimulation members 614 and at least a portionof the elongate body 602 can be deployed from the distal end 682 of thepulmonary artery catheter 691 during the delivery and implantation ofthe catheter 600.

The pulmonary artery catheter 691 can further include an inflatableballoon 668 on the peripheral surface 676 of the elongate catheter body670. The inflatable balloon 668 has a balloon wall 688 with an interiorsurface 690 that, along with a portion of the peripheral surface 676 ofthe elongate catheter body 670 defines a fluid tight volume 692. Thepulmonary artery catheter 691 further includes an inflation lumen 694that extends through the elongate catheter body 670, where the inflationlumen 694 has a first opening 696 into the fluid tight volume 692 of theinflatable balloon 668 and a second opening 698 proximal to the firstopening 696 to allow for a fluid to move in the fluid tight volume 692to inflate and deflate the balloon 668, for example as previouslydiscussed herein. The catheter system shown in FIG. 6 can be used toposition the catheter 600 in the main pulmonary artery and/or one orboth of the pulmonary arteries of the patient, for example as describedherein. The at least two elongate stimulation members 614 and the anchormember 636 can be repositioned within the lumen 694 of the pulmonaryartery catheter 691 by moving the elongate catheter body 670 relativethe elongate body 602 back over the at least two elongate stimulationmembers 614 and the anchor member 636. The catheter system illustratedin FIG. 6 can optionally include the positioning gauge, as discussed inconnection with FIGS. 4A and 4B, for example.

Referring now to FIGS. 7A and 7B, there is shown alternative embodimentsof a pulmonary artery catheter 791 that can be used with any of thecatheters described herein (e.g., catheter 300, 400, 500 or 600). Asillustrated, the pulmonary artery catheter 791 includes an elongatecatheter body 7100 with a first end 7102, a second end 7104, aperipheral surface 7106 and an interior surface 7108, opposite theperipheral surface 7106. The interior surface 7108 defines a lumen 7110that extends between the first end 7102 and the second end 7104 of theelongate catheter body 7100. The lumen 7110 is of a sufficient size andshape to house at least a portion of the catheter (e.g., catheter 300,400, 500 or 600) inside the lumen 7110 during delivery of the catheter.For example, the anchor member and the at least two elongate stimulationmembers, along with a least a portion of the elongate body, can bepositioned within the lumen 7110. The anchor member, the at least twoelongate stimulation members and at least a portion of the elongate bodycan be deployed from the distal end 7104 of the pulmonary arterycatheter 791 during the delivery and implantation of the catheter (e.g.,catheter 300, 400, 500 or 600).

The pulmonary artery catheter 791 includes an inflatable balloon 7112.As illustrated, the inflatable balloon 7112 is positioned on an elongateinflation catheter body 7300 that passes through a balloon lumen 7302.The balloon lumen 7302 is defined by lumen surface 7304 that can extendfrom the first end 7102 through the second end 7104 of the elongatecatheter body 7100. The balloon lumen 7302 has a cross-sectionaldimension that allows the elongate inflation catheter body 7300 tolongitudinally move within the balloon lumen 7302. As such, theinflatable balloon 7112 can be moved relative to the distal end 7104 ofthe pulmonary artery catheter 791.

The inflatable balloon 7112 has a balloon wall 7114 with an interiorsurface 7116 that along with a portion of a peripheral surface 7106 ofthe elongate inflation catheter body 7300 defines a fluid tight volume7116. The elongate inflation catheter body 7300 further includes aninflation lumen 7120 that extends through the elongate inflationcatheter body 7300, where the inflation lumen 7120 has a first opening7122 into the fluid tight volume 7116 of the inflatable balloon 7112 anda second opening 7124 proximal to the first opening 7122 to allow for afluid to move in the fluid tight volume 7116 to inflate and deflate theballoon 7112. A syringe, or other known devices, containing the fluid(e.g., saline or a gas (e.g., oxygen)) can be used to inflate anddeflate the balloon 7112. The cross-sectional dimension of the balloonlumen 7302 is also sufficient to allow the inflatable balloon 7112 inits fully deflated state to be housed within the lumen 7302. Theinflatable balloon 7112 along with at least a portion of the elongateinflation catheter body 7300 can be extended from the second end 7104when the inflatable balloon 7112 is to be inflated.

FIG. 7B illustrates an alternative embodiment of the pulmonary arterycatheter 791 that can be used with any of the catheters (e.g., catheters300, 400, 500, or 600) according to the present disclosure. As with thepulmonary artery catheter 791 illustrated in FIG. 7A, the pulmonaryartery catheter 791 includes an elongate catheter body 7100 with a firstend 7102, a second end 7104, a peripheral surface 7106 and an interiorsurface, opposite the peripheral surface 7106. The interior surfacedefines the lumen 7110 that extends between the first end 7102 and thesecond end 7104 of the elongate catheter body 7100. The lumen 7110 is ofa sufficient size and shape to house at least a portion of the catheter(e.g., catheter 300, 400, 500, or 600) inside the lumen 7110 duringdelivery of the catheter. For example, the anchor member and the atleast two elongate stimulation members, along with a least a portion ofthe elongate body, can be positioned within the lumen 7110 (theembodiment illustrated in FIG. 7B has the catheter (e.g., catheter 300,400, 500, or 600) fully inside the lumen 7110). The anchor member, theat least two elongate stimulation members and at least a portion of theelongate body can be deployed from the distal end 7104 of the pulmonaryartery catheter 791 during the delivery and implantation of the catheter(e.g., catheter 300, 400, 500, or 600).

The pulmonary artery catheter 791 illustrated in FIG. 7B includes twoinflatable balloons 7112 (shown as 7112-1 and 7112-2 in FIG. 7B). Asillustrated, each of the inflatable balloons 7112-1 and 7112-2 arepositioned on separate elongate inflation catheter bodies 7300-1 and7300-2, where each of the elongate inflation catheter bodies 7300-1 and7300-2 pass through a balloon lumen 7302-1 and 7302-2, respectively. Asillustrated, each balloon lumen 7302-1 and 7302-2 is defined by a lumensurface 7304-1 and 7304-2, respectively, which can extend from the firstend 7102 through the second end 7104 of the elongate catheter body 7100.The balloon lumens 7302-1 and 7302-2 each have a cross-sectionaldimension that allows the elongate inflation catheter body 7300-1 and7300-2 to longitudinally move within their respective balloon lumen7302-1 and 7302-2. As such, each of the inflatable balloons 7112-1and/or 7112-2 can be independently moved relative to the distal end 7104of the pulmonary artery catheter 791. As with FIG. 7A, thecross-sectional dimension of each balloon lumen 7302-1 and 7302-2 may besufficient to allow each respective inflatable balloon 7112-1 and 7112-2in its fully deflated state to be housed within each respective balloonlumen 7302-1 and 7302-2. Each inflatable balloon 7112-1 and 7112-2,along with at least a portion of the elongate inflation catheter body7300-1 and 7300-2, can independently be extended from the second end7104 when the inflatable balloon 7112-1 and/or 7112-2 is to be inflated.

Each of the inflatable balloons 7112-1 and 7112-2 has a balloon wall7114-1 and 7114-2 with an interior surface 7116-1 and 7116-2,respectively, which along with a portion of a peripheral surface 7106 ofthe elongate inflation catheter body 7300-1 and 7300-2 define a fluidtight volume 7118-1 and 7118-2, respectively. The elongate inflationcatheter body 7300 further includes an inflation lumen 7120-1 and 7120-2that extends through the elongate inflation catheter body 7300-1 and7300-2, respectively, where the inflation lumen 7120-1, 7120-2 has afirst opening 7122-1, 7122-2 into the fluid tight volume 7118-1, 7118-2of the inflatable balloon 7112-1 and 7112-2 and a second opening 7124-1and 7124-2 proximal to the first opening 7122-1 and 7122-2 to allow fora fluid (e.g., liquid or gas) to move in and out of the fluid tightvolume 7118-1 and 7118-2 to inflate and deflate the balloon 7112-1 and7112-2. Each of the inflatable balloons 7112-1 and 7112-2 can beindependently moved relative to the second end 7104 of the elongate body7100 as well as independently inflated, as discussed elsewhere herein.

The pulmonary artery catheter 791 further includes a positioning gauge752. The positioning gauge 752 includes an elongate gauge body 754 witha first end 756 and a bumper end 758 distal to the first end 756. Theelongate gauge body 754 can be moved longitudinally within a lumen 750defined by a surface that extends through the elongate catheter body7100. The elongate gauge body 754 extends through the lumen 750 of theelongate catheter body 7100 to position the bumper end 758 beyond thesecond end 7104 of the elongate catheter body 7100. The first end 756 ofthe position gauge 752 extends from the first end 7102 of the elongatecatheter body 7100, where the elongate gauge body 754 includes a markingthat indicates a length between the second end 7104 of the elongatecatheter body 7100 and the bumper end 758 of the position gauge 752.

The pulmonary artery catheter 791 can also include a first anchor 729that extends laterally from the peripheral surface 7106 of the elongatecatheter body 7100. As illustrated, the first anchor 729 has struts 731that form an open framework. The struts 731 have a peripheral surface733 having a largest outer dimension that allows the first anchor 729(when deployed) to engage a surface of the main pulmonary artery and/orone or both of the pulmonary arteries. A sheath can cover and hold thefirst anchor 729 in an undeployed state as the pulmonary artery catheter791 and the catheter (e.g., catheter 300, 400, 500, or 600) are beingintroduced into the patient.

The catheter system shown in FIGS. 7A and 7B can be used to position acatheter (e.g., catheter 300, 400, 500, and/or 600) in the mainpulmonary artery and/or one or both of the right and left pulmonaryarteries of the patient, for example as described herein. To accomplishthis, the pulmonary artery catheter 791 with the catheter positionedwithin the lumen 7110 is introduced into the vasculature through apercutaneous incision, and guided to the right ventricle (e.g., using aSwan-Ganz approach through an incision in the neck). For the cathetersystem of FIG. 7A, the balloon 7112 is inflated, as described, to allowthe pulmonary artery catheter 791 and the catheter to be carried by theflow of blood from the right ventricle to the main pulmonary artery orone of the right or left pulmonary arteries. Once the pulmonary arterycatheter 791 and the catheter (e.g., catheter 300, 400, 500, and/or 600)have been carried from the right ventricle into the main pulmonaryartery or one of the right or left pulmonary arteries the sheath can beretracted, thereby allowing the first anchor 729 to deploy within themain pulmonary artery. The first anchor 729 can be brought back into itsundeployed state by positioning the sheath (e.g., advancing the sheath)back over the first anchor 729.

With the first anchor 729 in its deployed position, the positioninggauge 752 can be used to determine a length between the second end 7104of the elongate catheter body 7100 and the top of the main pulmonaryartery (e.g., a location distal to the pulmonary valve and adjacent toboth the right and left pulmonary arteries). Knowing this length, thecatheter (e.g., catheter 300, 400, 500, 600) can be advanced from thelumen 7110 of the elongate catheter body 7100 to a location between thesecond end 7104 of the elongate catheter body 7100 and the top of themain pulmonary artery. This location can be determined, for example,using markings (e.g., markings providing a length in, for example,millimeters) on a portion of the elongate body of the catheter thatextends proximally from the first end 7102 of the elongate catheter body7100.

Referring now to FIGS. 8A through 8D, there is shown an additionalembodiment of a catheter 800 according to the present disclosure. Thecatheter 800 includes an elongate catheter body 801 having a first end803 and a second end 805. The elongate catheter body 801 also includes aperipheral surface 807 and an interior surface 809 defining an inflationlumen 811 (shown with a broken line) that extends at least partiallybetween the first end 803 and the second end 805 of the elongatecatheter body 801.

The catheter 800 includes an inflatable balloon 813 on the peripheralsurface 807 of the elongate catheter body 801. The inflatable balloon813 includes a balloon wall 815 with an interior surface 817 that, alongwith a portion of the peripheral surface 807 of the elongate catheterbody 801, defines a fluid tight volume 819. The inflation lumen 811includes a first opening 821 into the fluid tight volume 819 of theinflatable balloon 813 and a second opening 823 proximal to the firstopening 821 to allow for a fluid to move in and out of the volume 819 toinflate and deflate the balloon 813.

The catheter 800 further includes a plurality of electrodes 825positioned along the peripheral surface 807 of the elongate catheterbody 801. The plurality of electrodes 825 is located between theinflatable balloon 813 and the first end 803 of the elongate catheterbody 801. Conductive elements 827 extend through the elongate catheterbody 801, where the conductive elements 827 conduct electrical currentto combinations of two or more of the plurality of electrodes 825.

The catheter 800 further includes a first anchor 829 that extendslaterally from the peripheral surface 807 of the elongate body 801, thefirst anchor 829 having struts 831 forming an open framework. In theillustrated embodiment, the struts 831 have a peripheral surface 833having a largest outer dimension greater than the largest outerdimension of the inflatable balloon 813 (e.g., its largest diameter). Asillustrated, the first anchor 829 has a center point 835 relative to theperipheral surface 833 that is eccentric relative to a center point 837of the elongate catheter body 801 relative to the peripheral surface807.

FIGS. 8A and 8B both show the first anchor 829. FIG. 8A shows the firstanchor 829 positioned between the inflatable balloon 813 and theplurality of electrodes 825 positioned along the peripheral surface 807of the elongate catheter body 801. FIG. 8B shows the first anchor 829positioned between the plurality of electrodes 825 positioned along theperipheral surface 807 of the elongate catheter body 801 and the firstend 803 of the elongate catheter body 801.

For the catheter 800 shown in FIG. 8A, a portion 839 of the elongatecatheter body 801 that includes the plurality of electrodes 825 maycurve in a predefined radial direction when placed under longitudinalcompression. To achieve the curving of this portion 839 that includesthe plurality of electrodes 825, the elongate catheter body 801 can bepre-stressed and/or the wall can have thicknesses that allow for theelongate catheter body 801 to curve in the predefined radial directionwhen placed under longitudinal compression. In addition, oralternatively, structures such as coils or a helix of wire havingdifferent turns per unit length can be located within the elongatecatheter body 801 in the portion 839. One or more of these structurescan be used to allow the longitudinal compression to create the curve inthe predefined radial direction in the portion 839. To achieve thelongitudinal compression, the first anchor 829 can be deployed in thevasculature of the patient (e.g., in the pulmonary artery), where thefirst anchor 829 provides a location or point of resistance against thelongitudinal movement of the elongate body 801. As such, this allows acompressive force to be generated in the elongate catheter body 801sufficient to cause the portion 839 of the elongate catheter body 801along which the plurality of electrodes 825 are present to curve in thepredefined radial direction.

FIG. 8C provides an illustration of the portion 839 of the elongatecatheter body 801 curved in a predefined radial direction when placedunder longitudinal compression. The catheter 800 illustrated in FIG. 8Cis representative of the catheter shown in FIG. 8A and is describedherein. As illustrated, the catheter 800 has been at least partiallypositioned within the main pulmonary artery 8500 of a patient's heart(the catheter 800 can also be at least partially positioned within theright pulmonary artery 8504 as illustrated), where the balloon 813 andthe first anchor 829 are located in the lumen of the left pulmonaryartery 8502. From this position, a compressive force applied to theelongate catheter body 801 can cause the portion 839 of the elongatecatheter body 801 with the plurality of electrodes 825 to curve in thepredefined radial direction, thereby allowing (e.g., causing) theplurality of electrodes 825 to extend towards and/or touch the luminalsurface of the main pulmonary artery 8500. In accordance with severalembodiments, the plurality of electrodes 825 are brought into positionand/or contact with the luminal surface of the main pulmonary artery8500.

Providing a rotational torque at the first end 803 of the elongatecatheter body 801 can help to move the plurality of electrodes 825relative to the luminal surface, thereby allowing a professional orclinician to “sweep” the plurality of electrodes 825 into differentpositions along the luminal surface of the main pulmonary artery 8500.As discussed herein, this allows for the patient's cardiac response tothe stimulation electrical energy to be monitored and recorded at avariety of locations along the luminal surface of the main pulmonaryartery 8500. In this way, a preferred location for the position of theelectrodes 825 along the luminal surface of the main pulmonary artery8500 can be identified. In accordance with other embodiments, theplurality of electrodes 825 may be brought into position and/or contactwith the luminal surface of the left pulmonary artery 8502 or the rightpulmonary artery 8504 or at other locations, as desired and/or required.

Alternatively, for the catheter 800 shown in FIG. 8B, the elongatecatheter body 801 can include a second interior surface 841 defining ashaping lumen 843 that extends from the first end 803 towards the secondend 805. The catheter 800 of FIG. 8B can also include a shaping wire 845having a first end 847 and a second end 849. In one embodiment, theshaping lumen 843 has a size (e.g., a diameter) sufficient to allow theshaping wire 845 to pass through the shaping lumen 843 with the firstend 847 of the shaping wire 845 proximal to the first end 803 of theelongate catheter body 801 and the second end 849 of the shaping wire845 joined to the elongate catheter body 801 so that the shaping wire845 imparts a curve into the portion 839 of the elongate catheter body801 having the plurality of electrodes 825 when tension is applied tothe shaping wire 845.

FIG. 8D provides an illustration of the portion 839 of the elongatecatheter body 801 curved in a predefined radial direction when using theshaping lumen and shaping wire as discussed herein (the catheter 800illustrated in FIG. 8D is the catheter shown in FIG. 8B and is describedherein). As illustrated, the catheter 800 has been at least partiallypositioned within the main pulmonary artery 8500 of a patient's heart,where the balloon 813 is located in the lumen of the left pulmonaryartery 8502 and the first anchor 829 is located in the main pulmonaryartery 8500. From this position, the shaping wire 845 can be used toimpart the curve into the portion 839 of the elongate catheter body 801having the plurality of electrodes 825 when tension is applied to theshaping wire 845, thereby allowing (e.g., causing) the plurality ofelectrodes 825 to extend towards and/or touch the luminal surface of themain pulmonary artery 8500 (the catheter 800 can also be at leastpartially positioned within the right pulmonary artery 8504 asillustrated). In accordance with several embodiments, the plurality ofelectrodes 825 are brought into position and/or contact with the luminalsurface of the main pulmonary artery. In accordance with otherembodiments, the plurality of electrodes 825 may be brought intoposition and/or contact with the luminal surface of the left pulmonaryartery 8502 or the right pulmonary artery 8504 or at other locations, asdesired and/or required.

Providing a rotational torque at the first end 803 of the elongatecatheter body 801 can help to move the plurality of electrodes 825relative to the luminal surface of the main pulmonary artery 8500(and/or the right or left pulmonary artery), thereby allowing aprofessional or clinician to “sweep” the plurality of electrodes 825into different positions along the luminal surface of the main pulmonaryartery (and/or the right or left pulmonary artery), as discussed herein,so as to identify a preferred location for the position of theelectrodes 825 along the luminal surface of the main pulmonary artery(and/or the right or left pulmonary artery).

As illustrated, the catheter 800 of FIGS. 8A and 8B both include anelongate delivery sheath 851 having a lumen 853 that extends over aperipheral surface 807 of the elongate body 801. The elongate deliverysheath 851, in a first position, can have the first anchor 829positioned within the lumen 853 of the elongate delivery sheath 851. Asthe elongate delivery sheath 851 moves relative to the peripheralsurface 807 of the elongate body 801 the first anchor 829 extends fromthe peripheral surface 807 of the elongate body 801.

Referring now to FIG. 9 , there is shown an additional example of acatheter 900. As described for catheter 800, catheter 900 includes anelongate catheter body 901 having a first end 903 and a second end 905,a peripheral surface 907 and an interior surface 909 defining aninflation lumen 911 that extends at least partially between the firstend 903 and the second end 905 of the elongate catheter body 901. Thecatheter 900 includes an inflatable balloon 913 on the peripheralsurface 907 of the elongate catheter body 901, the inflatable balloon913 having a balloon wall 915 with an interior surface 917 that, alongwith a portion of the peripheral surface 907 of the elongate catheterbody 901, defines a fluid tight volume 919. The inflation lumen 911includes a first opening 921 into the fluid tight volume 919 of theinflatable balloon 913 and a second opening 923 proximal to the firstopening 921 to allow for a fluid (e.g., liquid or gas) to move in andout of the volume 919 to inflate and deflate the balloon 913.

The catheter 900 includes a plurality of electrodes 925 positioned alongthe peripheral surface 907 of the elongate catheter body 901. As shown,the plurality of electrodes 925 is located between the inflatableballoon 913 and the first end 903 of the elongate catheter body 901.Conductive elements 927 extend through the elongate catheter body 901,where the conductive elements 927 conduct electrical current tocombinations of one or more of the plurality of electrodes 925.

The catheter 900 further includes a first anchor 929 and a second anchor955 that both extend laterally from the peripheral surface 907 of theelongate body 901. Both the first anchor 929 and the second anchor 955have struts 931 that form an open framework for the anchors. The struts931 have a peripheral surface 933 having a largest outer dimensiongreater than the largest outer dimension of the inflatable balloon 913(e.g., its largest diameter). As illustrated, the first anchor 929 has acenter point 935 relative to the peripheral surface 933 that iseccentric relative to a center point 937 of the elongate catheter body901 relative to the peripheral surface 907. In contrast, the secondanchor 955 has a center point 935 relative to the peripheral surface 933that is concentric relative to the center point 937 of the elongatecatheter body 901 relative to the peripheral surface 907. In someembodiments, the first anchor 929 may have a center point 935 relativeto the peripheral surface 933 that is concentric relative to the centerpoint 937 of the elongate catheter body 901 relative to the peripheralsurface 907 and/or the second anchor 955 may have a center point 935relative to the peripheral surface 933 that is eccentric relative to acenter point 937 of the elongate catheter body 901 relative to theperipheral surface 907.

The catheter 900 includes an elongate delivery sheath 951 having a lumen953 that extends over a peripheral surface 907 of the elongate body 901.The elongate delivery sheath 951, in a first position, can have thefirst anchor 929 and the second anchor 955 positioned within the lumen953 of the elongate delivery sheath 951. As the elongate delivery sheath951 moves relative to the peripheral surface 907 of the elongate body901 the first anchor 929 extends from the peripheral surface 907 of theelongate body 901. As the elongate delivery sheath 951 moves furtheraway from the inflatable balloon 913 relative to the peripheral surface907, the second anchor 955 extends from the peripheral surface 907 ofthe elongate body 901.

As illustrated, the plurality of electrodes 925 are located between thefirst anchor 929 and the second anchor 955. A portion 939 of theelongate catheter body 901 that includes the plurality of electrodes 925can be made to curve in a predefined radial direction in a variety ofways. For example, the portion 939 of the elongate catheter body 901that includes the plurality of electrodes 925 can be made to curve inthe predefined radial direction when placed under longitudinalcompression (as discussed herein). As with the catheter 800, to causethe portion 939 that includes the plurality of electrodes 925 to curve,the elongate catheter body 901 can be pre-stressed and/or the wall canhave thicknesses that allow for the elongate catheter body 901 to curvein the predefined radial direction when placed under longitudinalcompression. In addition, or alternatively, structures such as coils ofa helix of wire having different turns per unit length can be locatedwithin the elongate catheter body 901 in the portion 939. One or more ofthese structures can be used to allow the longitudinal compression tocreate the curve in the predefined radial direction in the portion 939.

To achieve the longitudinal compression, the first anchor 929 can bedeployed in the vasculature of the patient, as discussed herein, wherethe first anchor 929 provides a location or point of resistance againstthe longitudinal movement of the elongate body 901. As discussed hereinfor example, this can be accomplished by moving the elongate deliverysheath 951 relative to the peripheral surface 907 of the elongate body901 so as to allow the first anchor 929 to extend from the peripheralsurface 907 of the elongate body 901. Once deployed, the first anchor929 allows a compressive force to be generated in the elongate catheterbody 901 sufficient to cause the portion 939 of the elongate catheterbody 901 along which the plurality of electrodes 925 are present tocurve in the predefined radial direction. Once the curve is formed inthe predefined radial direction, the elongate delivery sheath 951 ismoved further away from the inflatable balloon 913 relative to theperipheral surface 907 so as to allow the second anchor 955 to extendfrom the peripheral surface 907 of the elongate body 901.

Alternatively, the elongate catheter body 901 of the catheter 900 caninclude a second interior surface 941 defining a shaping lumen 943 thatextends from the first end 903 towards the second end 905. The catheter900 can also include a shaping wire 945 having a first end 947 and asecond end 949, where the shaping lumen 943 has a size (e.g., adiameter) sufficient to allow the shaping wire 945 to pass through theshaping lumen 943 with the first end 947 of the shaping wire 945proximal to the first end 903 of the elongate catheter body 901 and thesecond end 949 of the shaping wire 945 joined to the elongate catheterbody 901 so that the shaping wire 945 imparts a curve into the portion939 of the elongate catheter body 901 having the plurality of electrodes925 when tension is applied to the shaping wire 945.

Referring now to FIG. 10 , there is shown an additional embodiment ofthe catheter 1000. As discussed above, catheter 1000 includes anelongate catheter body 1001 having a first end 1003, a second end 1005,a peripheral surface 1007 and an interior surface 1009 defining aninflation lumen 1011 that extends at least partially between the firstend 1003 and the second end 1005 of the elongate catheter body 1001. Thecatheter 1000 also includes an inflatable balloon 1013 on the peripheralsurface 1007 of the elongate catheter body 1001, where the inflatableballoon 1013 has the balloon wall 1015 with an interior surface 1017that, along with a portion of the peripheral surface 1007 of theelongate catheter body 1001, defines a fluid tight volume 1019. Theinflation lumen 1011 includes a first opening 1021 into the fluid tightvolume 1019 of the inflatable balloon 1015 and a second opening 1023proximal to the first opening 1021 to allow for a fluid to move in andout of the volume 1019 to inflate and deflate the balloon 1015.

The elongate catheter body 1001 also includes a first anchor 1029 thatcan extend laterally from the peripheral surface 1007 of the elongatecatheter body 1001. As discussed herein, the first anchor 1029 includesstruts 1031 forming an open framework with a peripheral surface 1033having a largest outer dimension greater than the largest outerdimension of the inflatable balloon 1013 (e.g., its largest diameter).As illustrated, the first anchor 1029 has a center point 1035 relativeto the peripheral surface 1033 that is eccentric relative to a centerpoint 1037 of the elongate catheter body 1001 relative to the peripheralsurface 1007.

The catheter 1000 further includes an electrode catheter 1057 having anelectrode elongate body 1059 and a plurality of electrodes 1025positioned along a peripheral surface 1061 of the electrode elongatebody 1059. Conductive elements 1063 extend through and/or along theelectrode elongate body 1059 of the electrode catheter 1057, where theconductive elements 1063 conduct electrical current to combinations ofone or more of the plurality of electrodes 1025. As illustrated, thefirst anchor 1029 is positioned between the inflatable balloon 1013 andthe plurality of electrodes 1025 positioned along the peripheral surfaceof the electrode elongate body 1059.

The catheter 1000 further includes an attachment ring 1065 joined to theelectrode catheter 1057 and positioned around the peripheral surface1061 of the elongate catheter body 1001 proximal to both the firstanchor 1029 and the inflatable balloon 1013. In one embodiment, theattachment ring 1065 holds a distal end 1067 of the electrode catheter1057 in a static relationship to the elongate catheter body 1001. Fromthis position, a portion 1039 of the electrode elongate body 1059 thatincludes the plurality of electrodes 1025 can be made to curve in apredefined radial direction, as previously discussed. The configurationof the portion 1039 of the electrode elongate body 1059 that includesthe plurality of electrodes 1025 that curves can have any of theconfigurations and curvature mechanisms as discussed herein.

FIG. 10 also illustrates an elongate delivery sheath 1051 having a lumen1053 that extends over the peripheral surface of the elongate catheterbody 1001 and the electrode catheter 1057. The elongate delivery sheath1051, in a first position, can have the first anchor 1029 positionedwithin the lumen 1053 of the elongate delivery sheath 1051. As theelongate delivery sheath 1051 moves relative to the peripheral surface1007 of the elongate body 1001 and the peripheral surface 1061 of theelectrode catheter 1057, the first anchor 1029 extends from (e.g., awayfrom) the peripheral surface 1007 of the elongate body 1001.

Referring now to FIG. 11 , a catheter system 1169 is shown in accordancewith an embodiment of the disclosure. The catheter system 1169 includesan elongate catheter body 1102 having a first end 1104, a second end1106, a peripheral surface 1176 and an interior surface 1184 defining aninflation lumen 1194 that extends at least partially between the firstend 1104 and the second end 1106 of the elongate catheter body 1102. Theelongate catheter body 1102 includes an elongate radial axis 1108defined by an intersection of a first plane 1110 and a second plane 1112perpendicular to the first plane 1110, where the elongate radial axis1108 extends through the first end 1104 and the second end 1106 of theelongate catheter body 1102.

The catheter system 1169 further includes an inflatable balloon 1178 onthe peripheral surface 1176 of the elongate catheter body 1102. Theinflatable balloon 1178 has a balloon wall 1188 with an interior surface1190 that, along with a portion of the peripheral surface 1176 of theelongate catheter body 1102, defines a fluid tight volume 1192. Theinflation lumen 1194 includes a first opening 1196 into the fluid tightvolume 1192 of the inflatable balloon 1178 and a second opening 1198proximal to the first opening 1196 to allow for a fluid to move in andout of the volume 1192 to inflate and deflate the balloon 1178.

The catheter system 1169 further includes an electrode cage 11690 havingtwo or more ribs 1171 that extend radially away from the peripheralsurface 1176 of the elongate catheter body 1102 towards the inflatableballoon 1178. As illustrated, each of the ribs 1171 of the electrodecage 11690 have a first end 11692 that extends away from the elongatecatheter body 1101 towards the inflatable balloon 1178. Each of thefirst ends 11692 of the ribs 1171 of the electrode cage 11690 is freerelative to every other first end of the ribs 1171. In addition, theribs 1171 of the electrode cage 1169 curve into a first half 1116 of thefirst plane 1110. Each of the ribs 1171 of the electrode cage 1169 alsoincludes one or more electrodes 1125. The one or more electrodes 1125 oneach of the ribs 1171 form an electrode array on the first half 1116 ofthe first plane 1110. The catheter system 1169 further includesconductive elements 1120 extending through and/or along the ribs 1171 ofthe electrode cage 1169 and the elongate catheter body 1101, where theconductive elements 1120 conduct electrical current to combinations ofone or more electrodes 1125 in the electrode array.

The catheter system 1169 also includes an anchoring cage 1173 having twoor more of the ribs 1171 that extend radially away from the peripheralsurface 1176 of the elongate catheter body 1101 towards the inflatableballoon 1178. As illustrated, the two or more ribs 1171 of the anchoringcage 1173 curve into the second half 1134 of the first plane 1110. Inthe illustrated embodiment, the two or more ribs 1171 of the anchoringcage 1173 do not include any electrodes. In some embodiments, one ormore of the ribs 1171 of the anchoring cage 1173 include one or moreelectrodes.

The catheter system 1169 can further include a second inflatable balloonon the peripheral surface 1176 of the elongate catheter body 1101. Forexample, the elongate catheter body 1101 can further include a third endand a second interior surface defining a second inflation lumen thatextends at least partially between the first end and the third end ofthe elongate catheter body 1101. The second inflatable balloon may belocated on the peripheral surface 1176 of the elongate catheter body1101 adjacent the third end of the elongate catheter body 1101. As withthe first inflatable balloon 1178, the second inflatable balloon mayinclude a balloon wall with an interior surface that, along with aportion of the peripheral surface 1176 of the elongate catheter body1101, defines a fluid tight volume. The second inflation lumen mayinclude a first opening into the fluid tight volume of the secondinflatable balloon and a second opening proximal to the first opening toallow for a fluid to move in and out of the volume to inflate anddeflate the second balloon.

FIG. 11 also illustrates the elongate delivery sheath 1151 having alumen 1153 that extends over the peripheral surface of the elongatecatheter body 1101 and the ribs 1171 of both the electrode cage 1169 andthe anchoring cage 1173. The elongate delivery sheath 1151, in a firstposition, can have the ribs 1171 of both the electrode cage 1169 and theanchoring cage 1173 within the lumen 1153 of the elongate deliverysheath 1151. As the elongate delivery sheath 1151 moves relative to theperipheral surface 1107 of the elongate body 1101, the ribs 1171 of theelectrode cage 1169 extend from the elongate body 1101 to curve into thefirst half 1116 of the first plane 1110 and the ribs 1171 of theanchoring cage 1173 extend from the elongate body 1101 to curve into thesecond half 1134 of the first plane 1110.

Referring now to FIG. 12A, there is shown a perspective view of anembodiment of a catheter 1200. The catheter 1200 includes an elongatebody 1202 having a first end 1204 and a second end 1206 distal from thefirst end 1204. As illustrated, the elongate body 1202 includes alongitudinal center axis 1208 extending between the first end 1204 andthe second end 1206 of the elongate body 1202. The elongate body 1202also includes a portion 1210 that has three or more surfaces 1212defining a convex polygonal cross-sectional shape taken perpendicularlyto the longitudinal center axis 1208.

As used herein, the convex polygonal cross-sectional shape of theelongate body 1202 includes those shapes for which every internal angleis less than 180 degrees and where every line segment between twovertices of the shape remains inside or on the boundary of the shape.Examples of such shapes include, but are not limited to, triangular,rectangular (as illustrated in FIG. 12A), square, pentagon and hexagon,among others.

As illustrated, the catheter 1200 includes one or more (e.g., two ormore), electrodes 1214 on one surface of the three or more surfaces 1212of the elongate body 1202. Conductive elements 1216 extend throughand/or along the elongate body 1202, where the conductive elements 1216can be used, for example as discussed herein, to conduct electricalcurrent to combinations of the one or more electrodes 1214. Each of theone or more electrodes 1214 is coupled to a corresponding conductiveelement 1216. In some embodiments, the conductive elements 1216 areelectrically isolated from each other and extend through and/or alongthe elongate body 1202 from each respective electrode 1214 through thefirst end 1204 of the elongate body 1202. The conductive elements 1216may terminate at a connector port, where each of the conductive elements1216 can be releasably coupled to a stimulation system, such as thestimulation systems described herein. In some embodiments, theconductive elements 1216 are permanently coupled to the stimulationsystem (e.g., not releasably coupled). The stimulation system can beused to provide stimulation electrical energy that is conducted throughthe conductive elements 1216 and delivered across combinations of theone or more electrodes 1214. The one or more electrodes 1214 may beelectrically isolated from one another and the elongate body 1202 may beformed of an electrically insulating material as discussed herein. Asillustrated, the one or more electrodes 1214 are located only on the onesurface of the three or more surfaces 1212 of the elongate body 1202, inaccordance with one embodiment.

There can be a variety of the number and the configuration of the one ormore electrodes 1214 on the one surface of the three or more surfaces1212 of the elongate body 1202. For example, as illustrated, the one ormore electrodes 1214 can be configured as an array of electrodes, wherethe number of electrodes and their relative position to each other canvary depending upon the desired implant (e.g., deployment or target)location. As discussed herein, the one or more electrodes 1214 can beconfigured to allow for electrical current to be delivered from and/orbetween different combinations of the one or more electrodes 1214. So,for example, the electrodes in the array of electrodes can have arepeating pattern where the electrodes are equally spaced from eachother. For example, the electrodes in the array of electrodes can have acolumn and row configuration (as illustrated in FIG. 12A).Alternatively, the electrodes in the array of electrodes can have aconcentric radial pattern, where the electrodes are positioned so as toform concentric rings of the electrodes. Other patterns are possible,where such patterns can either be repeating patterns or random patterns.

As illustrated, the one or more electrodes 1214 have an exposed face1218. The exposed face 1218 of the electrode 1214 provides theopportunity for the electrode 1214, when implanted (temporarily or foran extended duration of time) in the patient, to be placed intoproximity and/or in contact with vascular tissue of the patient (e.g.,of the right or left pulmonary artery), as opposed to facing into thevolume of blood in the artery or other vessel, lumen or organ. As theone or more electrodes 1214 are located on one surface of the three ormore surfaces 1212 of the elongate body 1202, the electrodes 1214 can beplaced into direct proximity to and/or in contact with the tissue of anycombination of the main pulmonary artery, the left pulmonary arteryand/or the right pulmonary artery.

By locating the one or more electrodes 1214 on the one surface of thethree or more surfaces 1212, the exposed face 1218 of the electrode canbe positioned inside the patient's vasculature to face and/or contactthe tissue of the main pulmonary artery, the left pulmonary arteryand/or the right pulmonary artery. When the one or more electrodes 1214are in contact with luminal surface of the patient's vasculature, theone or more electrodes 1214 will be pointing away from the majority ofthe blood volume of that region of the pulmonary artery, therebyallowing the electrical pulses from the one or more electrodes 1214 tobe directed into the tissue adjacent the implant location, instead ofbeing directed into the blood volume.

The exposed face 1218 of the one or more electrodes 1214 can have avariety of shapes. For example, the exposed face 1218 can have a flatplanar shape. In this embodiment, the exposed face 1218 of theelectrodes 1214 can be co-planar with the one surface of the three ormore surfaces 1212 of the elongate body 1202. In an alternativeembodiment, the exposed face 1218 of the electrodes 1214 can have asemi-hemispherical shape. Other shapes for the exposed face 1218 of theelectrodes 1214 can include semi-cylindrical, wave-shaped, andzig-zag-shaped. The exposed face 1218 of the electrodes 1214 can alsoinclude one or more anchor structures. Examples of such anchorstructures include hooks that can optionally include a barb. Similarly,the electrodes 1214 can be shaped to also act as anchor structures.

In one embodiment, the one surface of the three or more surfaces 1112 ofthe elongate body 1102 that includes the exposed face 1218 of the one ormore electrodes 1214 can further include anchor structures 1220 thatextend above the one surface of the three or more surfaces 1212. Asillustrated, the anchor structures 1220 can include portions that cancontact the vascular tissue in such a way that the movement of the oneor more electrodes 1214 at the location where they contact the vasculartissue is reduced (e.g., minimized). The anchor structures 1220 can havea variety of shapes that may help to achieve this goal. For example, theanchor structures 1220 can have a conical shape, where the vertex of theconical shape can contact the vascular tissue. In one embodiment, theanchor structures 1220 have a hook configuration (with or without abarb). In an additional embodiment, one or more of the anchor structures1220 can be configured as an electrode.

As illustrated, the elongate body 1202 of the catheter 1200 can alsoinclude a portion 1222 with a circular cross-section shape takenperpendicularly to the longitudinal center axis 1208. The elongate body1202 of catheter 1200 also includes a surface 1224 defining a guide-wirelumen 1226 that extends through the elongate body 1202. The guide-wirelumen 1226 may have a diameter that is sufficiently large to allow theguide wire to freely pass through the guide-wire lumen 1226. Theguide-wire lumen 1226 can be positioned concentrically relative to thelongitudinal center axis 1208 of the elongate body 1202.

Alternatively, and as illustrated in FIG. 12A, the guide-wire lumen 126can be positioned eccentrically relative to the longitudinal center axis1208 of the elongate body 1202. When the guide-wire lumen 1226 ispositioned eccentrically relative to the longitudinal center axis 1208,the guide-wire lumen 1226 has a wall thickness 1228 takenperpendicularly to the longitudinal center axis that is greater than awall thickness 1230 of a remainder of the catheter taken perpendicularlyto the longitudinal center axis. For this configuration, the differencesin wall thickness 1228 and 1230 help to provide the elongate body 1202with a preferential direction in which to bend. For example, the wallthickness 1228 of the elongate body 1202 being greater than the wallthickness 1230 causes the side of the elongate body 1102 with thegreater wall thickness to preferentially have the larger radius ofcurvature when the elongate body 1102 bends, in accordance with severalembodiments. By positioning the exposed face 1218 of the one or moreelectrodes 1214 on the side of the elongate body 1202 having the greaterwall thickness (e.g., wall thickness 1228), the one or more electrodes1214 can be more easily and predictably brought into contact with theluminal surface of the vasculature in and around the main pulmonaryartery and at least one of the right and left pulmonary arteries.

The catheter 1200 shown in FIG. 12A can be positioned in the mainpulmonary artery and/or one or both of the left and right pulmonaryarteries of the patient, such as described herein. To accomplish this, apulmonary artery guide catheter is introduced into the vasculaturethrough a percutaneous incision and guided to the right ventricle usingknown techniques. For example, the pulmonary artery guide catheter canbe inserted into the vasculature via a peripheral vein of the arm (e.g.,as with a peripherally inserted central catheter), via a peripheral veinof the neck or chest (e.g., as with a Swan-Ganz catheter approach), or aperipheral vein of the leg (e.g., a femoral vein). Other approaches caninclude, but are not limited to, an internal jugular approach. Changesin a patient's electrocardiography and/or pressure signals from thevasculature can be used to guide and locate the pulmonary artery guidecatheter within the patient's heart. Once in the proper location, aguide wire can be introduced into the patient via the pulmonary arteryguide catheter, where the guide wire is advanced into the main pulmonaryartery and/or one of the pulmonary arteries (e.g., left and rightpulmonary arteries). Using the guide-wire lumen 1226, the catheter 1200can be advanced over the guide wire so as to position the catheter 1200in the main pulmonary artery and/or one or both of the left and rightpulmonary arteries of the patient, for example as described herein.Various imaging modalities can be used in positioning the guide wire ofthe present disclosure in the main pulmonary artery and/or one of theleft and right pulmonary arteries of the patient. Such imagingmodalities include, but are not limited to, fluoroscopy, ultrasound,electromagnetic, and electropotential modalities.

Using a stimulation system, such as the stimulation systems discussedherein, stimulation electrical energy (e.g., electrical current orpulses) can be delivered across combinations of one or more of theelectrodes 1214. In accordance with several embodiments describedherein, it is possible for the patient's cardiac response to thestimulation electrical energy to be monitored and recorded forcomparison to other subsequent tests. It is appreciated that for any ofthe catheters discussed herein any combination of electrodes, includingreference electrodes (as discussed herein) positioned within or on thepatient's body, can be used in providing stimulation to and sensingcardiac signals from the subject (e.g., patient).

FIG. 12B illustrates another embodiment of the catheter 1200. Thecatheter 1200 includes the features and components as discussed above, adiscussion of which is not repeated but the element numbers are includedin FIG. 12B with the understanding that the discussion of these elementsis implicit. In addition, the elongate body 1202 of the catheter 1200includes a serpentine portion 1232 proximal to the one or moreelectrodes 1214. When implanted (e.g., deployed) in the vasculature ofthe patient, the serpentine portion 1232 of the elongate body 1202 canact as a “spring” to absorb and isolate the movement of the one or moreelectrodes 1214 from the remainder of the elongate body 1202 of thecatheter 1200. Besides having a serpentine shape, the serpentine portion1232 can have a coil like configuration. Other shapes that achieve theobjective of absorbing and isolating the movement of the one or moreelectrodes 1214 from the remainder of the elongate body 1202 of thecatheter 1200 once implanted may also be used as desired and/orrequired. During delivery of the catheter 1200, the presence of theguide wire in the guide-wire lumen 1226 can help to temporarilystraighten the serpentine portion 1232 of the elongate body 1202.

Referring now to FIG. 12C, there is shown an additional embodiment ofthe catheter 1200 as provided herein. The catheter 1200 can include thefeatures and components as discussed above for the catheters describedin connection with FIGS. 12A and 12B, a discussion of which is notrepeated but the element numbers are included in FIG. 12C with theunderstanding that the discussion of these elements is implicit. Inaddition, the catheter 1200 of the present embodiment includes aninflatable balloon 1234. As illustrated, the elongate body 1202 includesa peripheral surface 1236, where the inflatable balloon 1234 is locatedon the peripheral surface 1236 of the elongate body 1202. The inflatableballoon 1234 includes a balloon wall 1238 with an interior surface 1240that, along with a portion 1242 of the peripheral surface 1236 of theelongate body 1202, defines a fluid tight volume 1244.

The elongate body 1202 further includes a surface 1245 that defines aninflation lumen 1246 that extends through the elongate body 1202. Theinflation lumen 1246 includes a first opening 1248 into the fluid tightvolume 1244 of the inflatable balloon 1234 and a second opening 1250proximal to the first opening 1248 to allow for a fluid to move in andout of the fluid tight volume 1244 to inflate and deflate the balloon1234. A syringe, or other known devices, containing the fluid (e.g.,saline or a gas (e.g., oxygen)) can be used to inflate and deflate theballoon 334.

The catheter 1200 shown in FIG. 12C can be positioned in the mainpulmonary artery and/or one or both of the right and left pulmonaryarteries of the patient, for example as described herein. As discussedherein, a pulmonary artery guide catheter is introduced into thevasculature through a percutaneous incision, and guided to the rightventricle. Once in the proper location, the balloon 1234 can beinflated, as described, to allow the catheter 1200 to be carried by theflow of blood from the right ventricle to the main pulmonary arteryand/or one of the pulmonary arteries. Additionally, various imagingmodalities can be used in positioning the catheter of the presentdisclosure in the main pulmonary artery and/or one of the pulmonaryarteries of the patient. Such imaging modalities include, but are notlimited to, fluoroscopy, ultrasound, electromagnetic, andelectropotential modalities.

The catheter 1200 can be advanced along the main pulmonary artery untilthe second end 1206 of the catheter 1200 contacts the top of the mainpulmonary artery (e.g., a location distal to the pulmonary valve andadjacent to both the pulmonary arteries). Once the second end 1206 ofthe catheter 1200 reaches the top of the main pulmonary artery thepulmonary artery guide catheter can be moved relative to the catheter1200 so as to deploy the catheter 1200 from the pulmonary artery guidecatheter.

Markings can be present on the peripheral surface of the catheter body1202, where the markings start and extend from the first end 1202towards the second end 1206 of the catheter body 1202. The distancebetween the markings can be of units (e.g., millimeters, inches, etc.),which can allow the length between the second end 1206 of the catheter1200 and the top of the main pulmonary artery to be determined.

The ability to measure this distance from the top of the main pulmonaryartery may be helpful in placing the one or more electrodes 1214 in adesired location (e.g., at a location within the main pulmonary artery).In addition to measuring the distance from which the second end 1206 ofthe elongate body 1202 is placed from the top of the main pulmonaryartery, the elongate body 1202 can also be used to identify, or map, anoptimal position for the one or more electrodes 1214 within thevasculature. For example, the second end 1206 of the elongate body 1202can be positioned at the desired distance from the top of the mainpulmonary artery using the markings on the peripheral surface of thecatheter body 1202.

Using the stimulation system, such as the stimulations systems discussedherein, stimulation electrical energy (e.g., electrical current orelectrical pulses) can be delivered across combinations of the one ormore electrodes 1214. It is possible for the patient's cardiac responseto the stimulation electrical energy to be monitored and recorded forcomparison to other subsequent tests. It is appreciated that for any ofthe catheters discussed herein any combination of electrodes, includingreference electrodes (as discussed herein) positioned within or on thepatient's body, can be used in providing stimulation to and sensingcardiac signals from the patient.

Referring now to FIG. 12D, there is shown an additional embodiment ofthe catheter 1200. The catheter 1200 can include the features andcomponents as the catheters discussed above in connection with FIGS.12A-12C, a discussion of which is not repeated but the element numbersare included in FIG. 12D with the understanding that the discussion ofthese elements is implicit. In addition, the catheter 1200 of thepresent embodiment includes a surface 1252 defining a deflection lumen1254. The deflection lumen 1254 includes a first opening 1256 and asecond opening 1258 in the elongate body 1202. In one embodiment, thesecond opening 1258 is opposite the one or more electrodes 1214 on onesurface of the three or more surfaces 1212 of the elongate body 1202.

The catheter 1200 further includes an elongate deflection member 1260.The elongate deflection member 1260 includes an elongate body 1261having a first end 1263 and a second end 1265. The elongate deflectionmember 1260 extends through the first opening 1256 to the second opening1258 of the deflection lumen 1254. The deflection lumen 1254 has a size(e.g., a diameter) sufficient to allow the deflection member 1260 topass through the deflection lumen 1254 with the first end 1263 of thedeflection member 1260 proximal to the first end 1204 of the elongatebody 1202 and the second end 1265 of the deflection member 1260extendable from the second opening 1258 of the deflection lumen 1254.Pressure applied from the first end 1263 of the deflection member 1260can cause the deflection member 1260 to move within the deflection lumen1254. For example, when pressure is applied to the deflection member1260 to move the first end 1263 of the deflection member 1260 towardsthe first opening 1256 of the deflection lumen 1254, the pressure causesthe second end 1265 of the deflection member 1260 to extend from thesecond opening 1258.

As generally illustrated, the elongate deflection member 1260 can beadvanced through the deflection lumen 1254 so that elongate deflectionmember 1260 extends laterally away from the one or more electrodes 1214on the one surface of the three or more surfaces 1212 of the elongatebody 1202. The elongate deflection member 1260 can be of a length andshape that allows the elongate deflection member 1260 to be extended adistance sufficient to bring the one or more electrodes 1214 intocontact with the vascular luminal surface (e.g., a posterior surface ofthe main pulmonary artery and/or one or both of the pulmonary arteries)with a variety of pressures. Optionally, the elongate deflection member1260 can be configured to include one or more of the electrodes 1214,such as discussed herein.

For the various embodiments, the elongate body 1261 of the deflectionmember 1260 is formed of a flexible polymeric material. Examples of suchflexible polymeric material include, but are not limited to, medicalgrade polyurethanes, such as polyester-based polyurethanes,polyether-based polyurethanes, and polycarbonate-based polyurethanes;polyamides, polyamide block copolymers, polyolefins such as polyethylene(e.g., high density polyethylene); and polyimides, among others.

In one embodiment, the elongate body 1261 of the elongate deflectionmember 1260 also includes one or more support wires. The support wirescan be encased in the flexible polymeric material of the elongate body1261, where the support wires can help to provide both column strengthand a predefined shape to the elongate deflection member 1260. Forexample, the support wires can have a coil shape that extendslongitudinally along the length of the elongate body 1261. In accordancewith several embodiments, the coil shape advantageously allows for thelongitudinal force applied near or at the first end 1263 of thedeflection member 1260 to be transferred through the elongate body 1261so as to laterally extend the second end 1265 of the deflection member1260 from the second opening 1258 of the deflection lumen 1254.

The support wires can also provide the deflection member 1260 with apredetermined shape upon laterally extending from the second opening1258 of the deflection lumen 1254. The predetermined shape can bedetermined to engage the luminal wall of the pulmonary artery in orderto bring the electrodes 1214 into contact with the vascular tissue. Thepredetermined shape and the support wires can also help to impartstiffness to the deflection member 1260 that is sufficient to maintainthe electrodes 1214 on the luminal wall of the pulmonary artery underthe conditions within the vasculature of the subject (e.g., patient).The support wires can be formed of a variety of metals or metal alloys.Examples of such metals or metal alloys include surgical grade stainlesssteel, such as austenitic 316 stainless among others, and the nickel andtitanium alloy known as Nitinol. Other metals and/or metal alloys can beused as desired and/or required.

The catheter 1200 shown in FIG. 12D can be positioned in the mainpulmonary artery and/or one or both of the left and right pulmonaryarteries of the patient, such as described herein. In accordance withseveral methods, a pulmonary artery guide catheter is introduced intothe vasculature through a percutaneous incision, and guided to the rightventricle (e.g., using a Swan-Ganz catheterization approach). Once inthe proper location, the balloon 1234 can be inflated, as described, toallow the catheter 1200 to be carried by the flow of blood from theright ventricle to the main pulmonary artery and/or one of the right andleft pulmonary arteries. Additionally, various imaging modalities can beused in positioning the catheter in the main pulmonary artery and/or oneof the right and left pulmonary arteries of the patient. Such imagingmodalities include, but are not limited to, fluoroscopy, ultrasound,electromagnetic, and electropotential modalities.

The catheter 1200 can be advanced along the main pulmonary artery untilthe second end 1206 of the catheter 1200 contacts the top of the mainpulmonary artery (e.g., a location distal to the pulmonary valve andadjacent to both the pulmonary arteries). Once the second end 1206 ofthe catheter 1200 reaches the top of the main pulmonary artery thepulmonary artery guide catheter can be moved relative to the catheter1200 so as to deploy the catheter 1200 from the pulmonary artery guidecatheter.

Markings, as discussed herein, can be present on the peripheral surfaceof the catheter body 1202 that can assist in positioning the catheter1200 within the main pulmonary artery. The ability to measure thisdistance from the top of the main pulmonary artery may be helpful inplacing the one or more electrodes 1214 in a desired location (e.g., alocation within the main pulmonary artery). In addition to measuring thedistance from which the second end 1206 of the elongate body 1202 isplaced from the top of the main pulmonary artery, the elongate body 1202can also be used to identify, or map, an optimal position for the one ormore electrodes 1214 within the vasculature. For example, the second end1206 of the elongate body 1202 can be positioned at the desired distancefrom the top of the main pulmonary artery using the markings on theperipheral surface of the catheter body 1202.

When desired, the elongate deflection member 1260 can be extendedlaterally from the elongate body 1202 to a distance sufficient to causethe one surface of the three or more surfaces 1212 of the elongate body1202 having the one or more electrodes to contact a surface of the mainpulmonary artery, such as the anterior surface of the main pulmonaryartery, and thereby bring the one or more electrodes 1214 into contactwith the main pulmonary artery or one of the pulmonary arteries (theleft pulmonary artery or the right pulmonary artery). The elongatedeflection member 1260, as will be appreciated, biases and helps toplace the one or more electrodes 1214 along the vessel surface (e.g.,along the posterior surface of the main pulmonary artery or one of thepulmonary arteries (the left pulmonary artery or the right pulmonaryartery)).

Due to its adjustable nature (e.g., how much pressure is applied to theelongate deflection member 1260), the elongate deflection member 1260can be used to bring the one or more electrodes 1214 into contact withthe luminal surface of the main pulmonary artery or one of the pulmonaryarteries with a variety of pressures. So, for example, the elongatedeflection member 1260 can bring the one or more electrodes 1214 intocontact with the luminal surface of the main pulmonary artery or one ofthe left and right pulmonary arteries with a first pressure. Using thestimulation system, such as the stimulation systems discussed herein,stimulation electrical energy (e.g., electrical current or electricalpulses) can be delivered across combinations of the one or moreelectrodes 1214 in the electrode array. It is possible for the patient'scardiac response to the stimulation electrical energy to be monitoredand recorded for comparison to other subsequent tests.

It is appreciated that for any of the catheters discussed herein anycombination of electrodes, including reference electrodes (as discussedherein) positioned within or on the patient's body, can be used inproviding stimulation to and sensing cardiac signals from the patient.

If necessary, the distance the elongate deflection member 1260 extendslaterally from the elongate body 1202 can be changed (e.g., madeshorter) to allow the elongate body 1202 to be rotated in either aclockwise or counter-clockwise direction, thereby repositioning the oneor more electrodes 1214 in contact with the luminal surface of the mainpulmonary artery or one of the pulmonary arteries. The stimulationsystem can again be used to deliver stimulation electrical energy acrosscombinations of one or more of the electrodes 1214 in the electrodearray. The patient's cardiac response to this subsequent test can thenbe monitored and recorded for comparison to previous and subsequenttest. In this way, a preferred location for the position of the one ormore electrodes 1214 along the luminal surface of the main pulmonaryartery or one of the left and right pulmonary arteries can beidentified. Once identified, the elongate deflection member 1260 can beused to increase the lateral pressure applied to the one or moreelectrodes, thereby helping to better anchor the catheter 1200 in thepatient.

FIG. 13 provides a perspective view of a catheter 1330 positioned in theheart 200 of the subject (e.g., patient), where one or more of theelectrodes 1344 is contacting the posterior surface 221 and/or superiorsurface 223 of, for example, the right pulmonary artery 206. FIG. 13also illustrates the one or more of the electrodes 1344 contacting theposterior surface 221 and/or superior surface 223 of the right pulmonaryartery 208 at a position that is superior to the branch point 207. FIG.13 further illustrates that at least a portion of the catheter 1330 ispositioned in contact with a portion of the surface defining the branchpoint 207.

As illustrated, the pulmonary trunk has a diameter 1356 taken across aplane 1358 perpendicular to both the left lateral plane 220 and theright lateral plane 216. In one embodiment, the electrode array of thecatheter 1330 is positioned in an area 1360 that extends distally nomore than three times the diameter of the pulmonary trunk 202 to theright of the branch point 207. This area 1360 is shown withcross-hatching in FIG. 13 .

The right pulmonary artery 206 can also include a branch point 1362 thatdivides the right pulmonary artery 206 into at least two additionalarteries 1364 that are distal to the branch point 207 defining the leftpulmonary artery 208 and the right pulmonary artery 206. As illustrated,the electrode array can be positioned between the branch point 207defining the left pulmonary artery 208 and the right pulmonary artery206 and the branch point 1362 that divides the right pulmonary artery206 into at least two additional arteries 1364.

Once in position, electrical current can be provided from or to one ormore of the electrodes 1344. Using a first sensor 1352 a value of anon-cardiac parameter of the patient can be measured in response to theelectrical current from or to one or more of the electrodes 1344. Fromthe value of the non-cardiac parameter, changes can be made to which ofthe one or more electrodes are used to provide the electrical current inresponse to the value of the cardiac parameter. Changes can also be madeto the nature of the electrical current provided in response to thevalue of the non-cardiac parameter. Such changes include, but are notlimited to, changes in voltage, amperage, waveform, frequency and pulsewidth by way of example. It is possible to change combinations ofelectrodes used and the nature of the electrical current provided by theelectrodes. In addition, the electrodes of the one or more electrodes onthe posterior surface of the right pulmonary artery 206 can be moved inresponse to one or more of the values of the non-cardiac parameter.Examples of such a cardiac parameter include, but are not limited to,measuring a pressure parameter, an acoustic parameter, an accelerationparameter and/or an electrical parameter (e.g., ECG) of the heart of thepatient as the cardiac parameter. An example of such a pressureparameter can include, but is not limited to, measuring a maximumsystolic pressure of the heart of the patient as the pressure parameter.Other suitable cardiac parameters are discussed herein.

Moving the electrodes of the one or more electrodes on the posteriorand/or superior surface of the right pulmonary artery 206 in response toone or more of the values of the cardiac parameter can be done byphysically moving the one or more electrodes of the catheter 1330 to adifferent position on the posterior and/or superior surface of the rightpulmonary artery 206, electronically moving which electrodes of the oneor more electrodes are being used to provide the electrical current fromor to the electrode array (while not physically moving the one or moreelectrodes of the catheter 1330) or a combination of these two actions.

As discussed herein, neuromodulation according to the present disclosurecan be accomplished by applying electrical current to the rightpulmonary artery 206.

Preferably, neuromodulation of the present disclosure includes applyingthe electrical current to the posterior and/or superior wall of theright pulmonary artery 206. The electrical current is thereby applied tothe autonomic cardiopulmonary nerves surrounding the right pulmonaryartery 206. These autonomic cardiopulmonary nerves can include the rightautonomic cardiopulmonary nerves and the left autonomic cardiopulmonarynerves. The right autonomic cardiopulmonary nerves include the rightdorsal medial cardiopulmonary nerve and the right dorsal lateralcardiopulmonary nerve. The left autonomic cardiopulmonary nerves includethe left ventral cardiopulmonary nerve, the left dorsal medialcardiopulmonary nerve, the left dorsal lateral cardiopulmonary nerve,and the left stellate cardiopulmonary nerve.

As illustrated and discussed in reference to FIG. 13 , the one or moreelectrodes of the catheter are contacting the posterior surface of theright pulmonary artery 206. From this location, the electrical currentdelivered through the one or more electrodes may be better able to treatand/or provide therapy (including adjuvant therapy) to the patientexperiencing a variety of cardiovascular medical conditions, such asacute heart failure. The electrical current can elicit responses fromthe autonomic nervous system that may help to modulate a patient'scardiac contractility. The electrical current is intended to affectheart contractility more than the heart rate, thereby helping toimproving hemodynamic control while possibly minimizing unwantedsystemic effects.

Referring now to FIG. 14A, there is shown an additional embodiment of acatheter 1462. The catheter 1462 includes an elongate body 1402 having aperipheral surface 1436 and a longitudinal center axis 1408 extendingbetween a first end 1404 and a second end 1406. The catheter 1462 caninclude the features and components as discussed above for catheters100, 200, 300 and/or 400, a discussion of which is not repeated but theelement numbers are included in FIG. 14A with the understanding that thediscussion of these elements is implicit.

The catheter 1462 of the present embodiment includes an inflatableballoon 1434. As illustrated, the elongate body 1402 includes aperipheral surface 1436, where the inflatable balloon 1434 is located onthe peripheral surface 1436 of the elongate body 1402. The inflatableballoon 1434 includes a balloon wall 1438 with an interior surface 1440that along with a portion 1442 of the peripheral surface 1436 of theelongate body 1402 defines a fluid tight volume 1444.

The elongate body 1402 further includes a surface 1445 that defines aninflation lumen 1446 that extends through the elongate body 1402. Theinflation lumen 1446 includes a first opening 1448 into the fluid tightvolume 1444 of the inflatable balloon 1434 and a second opening 1450proximal to the first opening 1448 to allow for a fluid to move in thefluid tight volume 1444 to inflate and deflate the balloon 1434. Asyringe, or other known devices, containing the fluid (e.g., saline or agas (e.g., oxygen)) can be used to inflate and deflate the balloon 1434.

The elongate body 1402 further includes an offset region 1464 defined bya series of predefined curves along the longitudinal center axis 1408.As used herein, “predefined curves” are curves formed in the elongatebody 1402 during the production of the catheter 1462, where whendeformed such curves provide a spring like force to return to theirpre-deformation shape (e.g., their original shape). As illustrated, theseries of predefined curves includes a first portion 1466 that has afirst curve 1468 in the longitudinal center axis 1408 followed by asecond curve 1470 in the longitudinal center axis 1408 of the elongatebody 1402. The length and degree of each of the first curve 1468 andsecond curve 1470, along with the distance between such curves, helps todefine the height of the offset region 1464. As discussed herein, theheight of the offset region 1464 can be determined by the inner diameterof one or more locations along the main pulmonary artery and/or one ofthe right and left pulmonary arteries.

The first portion 1466 of the elongate body 1402 is followed by a secondportion 1472 of the elongate body 1402. The longitudinal center axis1408 along the second portion 1472 can have a zero curvature (e.g., astraight line), as illustrated in FIG. 14A. The second portion 1472 ofthe elongate body 1402 is followed by a third portion 1474 of theelongate body 1402. The longitudinal center axis 1408 transitions fromthe second portion 1472 along a third curve 1476, which then transitionsinto a fourth curve 1478. As illustrated, after the fourth curve 1478,the longitudinal center axis 1408 is approximately co-linear with thelongitudinal center axis 1408 leading up to the first curve 1468. It isnoted that the curves of the first portion 1466 and the second portion1474 can also all be in approximately the same plane. It is, however,possible that the curves of the first portion 1466 and the secondportion 1474 are not in the same plane. For example, when the curves ofthe first portion 1466 and the second portion 1474 are not in the sameplane the longitudinal center axis 1408 can include a helical curvethrough these portions of the elongate body 1402. Other shapes are alsopossible.

The elongate body 1402 can further include one or more electrodes 1414,for example as discussed herein, along the second portion 1472 of theoffset region 1464 of the elongate body 1402. As illustrated, the one ormore electrodes 1414 can be on the surface of the elongate body 1402 inthe second portion 1472 of the offset region 1464. Conductive elements1416 extend through and/or along the elongate body 1402, where theconductive elements 1416 can be used, as discussed herein, to conductelectrical current to combinations of the one or more electrodes 1414.Each of the one or more electrodes 1414 is coupled to a correspondingconductive element 1416. The conductive elements 1416 are electricallyisolated from each other and extend through and/or along the elongatebody 1402 from each respective electrode 1414 through the first end 1404of the elongate body 1402. The conductive elements 1416 terminate at aconnector port, where each of the conductive elements 1416 can bereleasably coupled to a stimulation system, for example as discussedherein. It is also possible that the conductive elements 1416 arepermanently coupled to the stimulation system (e.g., not releasablycoupled). The stimulation system can be used to provide stimulationelectrical energy (e.g., electrical current or electrical pulses) thatis conducted through the conductive elements 1416 and delivered acrosscombinations of the one or more electrodes 1414. In some embodiments,the one or more electrodes 1414 are electrically isolated from oneanother, where the elongate body 1402 is formed of an electricallyinsulating material.

There can be wide variety for the number and configuration of the one ormore electrodes 1414 on the one surface of the second portion 1472 ofthe elongate body 1402. For example, as illustrated, the one or moreelectrodes 1414 can be configured as an array of electrodes, where thenumber of electrodes and their relative position to each other can varydepending upon the desired implant location. As discussed herein, theone or more electrodes 1414 can be configured to allow for electricalcurrent to be delivered from and/or between different combinations ofthe one or more electrodes 1414. The electrodes in the array ofelectrodes can have a repeating pattern where the electrodes are equallyspaced from each other. So, for example, the electrodes in the array ofelectrodes can have a column and row configuration. Alternatively, theelectrodes in the array of electrodes can have a concentric radialpattern, where the electrodes are positioned so as to form concentricrings of the electrodes. Other patterns are possible, where suchpatterns can either be repeating patterns or random patterns. Asdiscussed herein, the catheter 1462 further includes conductive elements1416 extending through and/or along the elongate body, where theconductive elements 1416 conduct electrical current to combinations ofthe one or more electrodes 1414.

As discussed herein, the length and degree of each of the curves, alongwith the distance between such curves helping to define the firstportion 1466 and the third portion 1474 of the longitudinal center axis1408, helps to define the relative height of the offset region 1464. Forthe various embodiments, the height of the offset region 1464 can bedetermined by the inner diameter of one or more locations along the mainpulmonary artery and/or one of the right and left pulmonary arteries. Inthis way, the first portion 1466 and the third portion 1474 can bringthe second portion 1472 and the one or more electrodes 1414 on thesurface of the elongate body 1402 into contact with the vascular wall ofthe patient in the main pulmonary artery and/or one of the left or rightpulmonary arteries. In other words, the transitions of the first portion1466 and the third portion 1474 of the elongate body 1402 in the offsetregion 1464 can act to bias the second portion 1472 and the one or moreelectrodes 1414 against the vascular wall of the patient in the mainpulmonary artery and/or one of the right or left pulmonary arteries.

The elongate body 1402 further includes a surface 1424 defining aguide-wire lumen 1426 that extends through and/or along the elongatebody 1402. As provided herein, the guide-wire lumen 1426 can beconcentric relative to the longitudinal center axis 1408 of the elongatebody 1402 (as illustrated in FIG. 14A). Alternatively, the guide-wirelumen 1426 can be eccentric relative to the longitudinal center axis1408 of the elongate body 1402. As discussed herein, the guide-wirelumen 1426 can have a wall thickness 1428 that is greater than a wallthickness 1430 of a remainder of the catheter 1462 taken perpendicularlyto the longitudinal center axis 1408. In an additional embodiment, aportion of the elongate body 1402 includes a serpentine portion, asdiscussed and illustrated herein, proximal to the one or more electrodes1414.

For the present embodiment, a guide-wire used with the catheter 1462 canserve to temporarily “straighten” the offset region 1464 when theguide-wire is present in the guide-wire lumen 1426 that passes along theoffset region 1464. Alternatively, the guide-wire can be used to impartthe shape of the offset region 1464 to the catheter 1462. In thisembodiment, the elongate body 1402 of the catheter 1462 can have astraight shape (e.g., no predefined lateral shape). To impart the offsetregion 1464 the guide wire is “shaped” (e.g., bent) to the desiredconfiguration of the offset region at point that corresponds to thedesired longitudinal location for the offset region on the elongate body1402. The offset region 1464 of the catheter 1462 can be provided byinserting the guide wire with the predefined lateral shape.

In FIG. 14A, the catheter 1462 of the present embodiment furtherincludes a surface 1452 defining a deflection lumen 1454, as discussedherein. The catheter 1462 further includes an elongate deflection member1460, also as discussed herein. As generally illustrated, the elongatedeflection member 1460 can be advanced through the deflection lumen 1454so that elongate deflection member 1460 extends laterally away from theone or more electrodes 1414 on the second portion 1472 of the elongatebody 1402. The elongate deflection member 1460 can be of a length andshape that allows the elongate deflection member 1460 to be extended adistance sufficient to bring the one or more electrodes 1414 intocontact with the vascular luminal surface (e.g., a posterior surface ofthe main pulmonary artery and/or one or both of the pulmonary arteries)with a variety of pressures.

In one embodiment, the elongate body 1461 of the elongate deflectionmember 1460 can also include one or more support wires 1481. The supportwires 1481 can be encased in the flexible polymeric material of theelongate body 1461, where the support wires 1481 can help to provideboth column strength and a predefined shape to the elongate deflectionmember 1460. For example, the support wires 1481 can have a coil shapethat extends longitudinally along the length of the elongate body 1461.In accordance with several embodiments, the coil shape advantageouslyallows for the longitudinal force applied near or at the first end 1463of the deflection member 1460 to be transferred through the elongatebody 1461 so as to laterally extend the second end 1465 of thedeflection member 1460 from the second opening 1458 of the deflectionlumen 1454.

The support wires 1481 can also provide the deflection member 1460 witha predetermined shape upon laterally extending from the second opening1458 of the deflection lumen 1454. The predetermined shape can bedetermined to engage the luminal wall of the pulmonary artery in orderto bring the electrodes 1414 on the second portion 1472 of the offsetregion 1464 into contact with the vascular tissue. The predeterminedshape and the support wires 1481 can also help to impart stiffness tothe deflection member 1460 that is sufficient to maintain the electrodes1414 on the luminal wall of the pulmonary artery under the conditionswithin the vasculature of the patient.

The support wires 1481 can be formed of a variety of metals or metalalloys. Examples of such metals or metal alloys include surgical gradestainless steel, such as austenitic 316 stainless among others, and thenickel and titanium alloy known as Nitinol. Other metals and/or metalalloys can be used as desired and/or required.

Referring now to FIG. 14B, there is shown an additional embodiment of acatheter 1462. The catheter 1462 can include the features and componentsof the catheters described above in connection with FIGS. 12A-12D and/or14A, a discussion of which is not repeated but the element numbers areincluded in FIG. 14B with the understanding that the discussion of theseelements is implicit.

The catheter 1462 seen in FIG. 14B is similar to the catheter 1462 ofFIG. 14A, where the elongate body 1402 of catheter 1462 further includesthree or more surfaces 1412 defining a convex polygonal cross-sectionalshape taken perpendicularly to the longitudinal center axis 1408, asdiscussed for the catheters 1200 herein. As illustrated, the one or moreelectrodes 1414 are on one surface of the three or more surfaces 1412 ofthe elongate body 1402. In the present embodiment, the three or moresurfaces 1412 of the elongate body 1402 help to form the second portion1472 of the elongate body 1402. If desired, the elongate body 1402 canincludes a serpentine portion proximal to the one or more electrodes1414.

Referring now to FIG. 15A, there is shown an additional embodiment of acatheter 1582 according to the present disclosure. The catheter 1582 caninclude the features and components of the catheters described above inconnection with FIGS. 12A-12D, 14A and/or 14B, a discussion of which isnot repeated but the element numbers are included in FIG. 15A with theunderstanding that the discussion of these elements is implicit.

The catheter 1582 includes an elongate body 1502 having a peripheralsurface 1536 and a longitudinal center axis 1508 extending between afirst end 1504 and a second end 1506. The elongate body 1502 includes asurface 1552 defining a deflection lumen 1554, where the deflectionlumen 1554 includes a first opening 1556 and a second opening 1558 inthe elongate body 1502. The catheter 1582 further includes an inflatableballoon 1534 on the peripheral surface 1536 of the elongate body 1502,the inflatable balloon 1534 having a balloon wall 1538 with an interiorsurface 1540 that along with a portion 1542 of the peripheral surface1536 of the elongate body 1502 defines a fluid tight volume 1544, suchas previously discussed herein. An inflation lumen 1546 extends throughthe elongate body 1502, where the inflation lumen 1546 has a firstopening 1548 into the fluid tight volume 1544 of the inflatable balloon1534 and a second opening 1550 proximal to the first opening 1548 toallow for a fluid (e.g., liquid or gas) to move in and out of the fluidtight volume 1544 to inflate and deflate the balloon 1534.

One or more electrodes 1514 are on the elongate body 1502, where thesecond opening 1558 of the deflection lumen 1554 is opposite the one ormore electrodes 1514 on the elongate body 1502. The catheter 1582further includes an elongate deflection member 1560, as discussedherein, where the elongate deflection member 1560 extends through thesecond opening 1558 of the deflection lumen 1554 in a direction oppositethe one or more electrodes 1514 on one surface of the elongate body1502. The catheter 1582 also includes conductive elements 1516 thatextend through and/or along the elongate body 1502, where the conductiveelements 1516 conduct electrical current to combinations of the one ormore electrodes 1514.

The catheter 1582 further includes a surface 1524 defining a guide-wirelumen 1526 that extends through and/or along the elongate body 1502. Asillustrated, the guide-wire lumen 1526 is concentric relative to thelongitudinal center axis 1508. As discussed herein, the guide-wire lumen1526 could also be eccentric relative to longitudinal center axis 1508of the elongate body 1508. Such embodiments are discussed herein, wherethe guide-wire lumen 1526 can have a wall thickness takenperpendicularly to the longitudinal center axis 1508 that is greaterthan a wall thickness of a remainder of the catheter 1582 takenperpendicularly to the longitudinal center axis 1508. The catheter 1582can also include a serpentine portion of the elongate body 1502 proximalto the one or more electrodes 1514.

Referring now to FIG. 15B, there is shown an additional embodiment of acatheter 1582. The catheter 1582 can include the features and componentsdescribed above in connection with FIGS. 12A-12D, 14A, 14B and/or 15A, adiscussion of which is not repeated but the element numbers are includedin FIG. 15B with the understanding that the discussion of these elementsis implicit.

The catheter 1582 includes an elongate body 1502 having a peripheralsurface 1536 and a longitudinal center axis 1508 extending between afirst end 1504 and a second end 1506. The elongate body 1502 includes asurface 1552 defining a deflection lumen 1554, where the deflectionlumen 1554 includes a first opening 1556 and a second opening 1558 inthe elongate body 1502. The catheter 1582 further includes an inflatableballoon 1534 on the peripheral surface 1536 of the elongate body 1502,the inflatable balloon 1534 having a balloon wall 1538 with an interiorsurface 1540 that along with a portion 1542 of the peripheral surface1536 of the elongate body 1502 defines a fluid tight volume 1544, asdiscussed herein. An inflation lumen 1546 extends through the elongatebody 1502, where the inflation lumen 1546 has a first opening 1548 intothe fluid tight volume 1544 of the inflatable balloon 1534 and a secondopening 1550 proximal to the first opening 1548 to allow for a fluid(e.g., gas or liquid) to move in and out of the fluid tight volume 1544to inflate and deflate the balloon 1534.

One or more electrodes 1514 are on the elongate body 1502, where thesecond opening 1558 of the deflection lumen 1554 is opposite the one ormore electrodes 1514 on the elongate body 1502. As illustrated, theelongate body 1502 has three or more surfaces 1512 defining a convexpolygonal cross-sectional shape taken perpendicularly to thelongitudinal center axis 1508. The one or more electrodes 1514 are onone surface of the three or more surfaces 1512 of the elongate body1502, such as discussed previously herein.

The catheter 1582 further includes an elongate deflection member 1560,where the elongate deflection member 1560 extends through the secondopening 1558 of the deflection lumen 1554 in a direction opposite theone or more electrodes 1514 on one surface of the elongate body 1502.The catheter 1582 also includes conductive elements 1516 that extendthrough and/or along the elongate body 1502, where the conductiveelements 1516 conduct electrical current to combinations of the one ormore electrodes 1514.

The catheter 1582 further includes a surface 1524 defining a guide-wirelumen 1526 that extends through and/or along the elongate body 1502. Asillustrated, the guide-wire lumen 1526 is concentric relative to thelongitudinal center axis 1508. As discussed herein, the guide-wire lumen1526 could also be eccentric relative to longitudinal center axis 1508of the elongate body 1502. Such embodiments are discussed herein, wherethe guide-wire lumen 1526 can have a wall thickness takenperpendicularly to the longitudinal center axis 1508 that is greaterthan a wall thickness of a remainder of the catheter 1582 takenperpendicularly to the longitudinal center axis 1508. The catheter 1582can also include a serpentine portion of the elongate body 1502 proximalto the one or more electrodes 1514.

Referring now to FIG. 16 , there is shown an additional embodiment of acatheter 1684. The catheter 1684 can include the features and componentsof the catheters described above in connection with FIGS. 12A-12D, 14A,14B, 15A and/or 15B, a discussion of which is not repeated but theelement numbers are included in FIG. 16 with the understanding that thediscussion of these elements is implicit.

The catheter 1684 includes an elongate body 1602 having a peripheralsurface 1636 and a longitudinal center axis 1608 extending between afirst end 1604 and a second end 1606. The catheter 1684 further includesan inflatable balloon 1634 on the peripheral surface 1636 of theelongate body 1602, the inflatable balloon 1634 having a balloon wall1638 with an interior surface 1640 that along with a portion 1642 of theperipheral surface 1636 of the elongate body 1602 defines a fluid tightvolume 1644, as discussed herein. An inflation lumen 1646 extendsthrough the elongate body 1602, where the inflation lumen 1646 has afirst opening 1648 into the fluid tight volume 1644 of the inflatableballoon 1634 and a second opening 1650 proximal to the first opening1648 to allow for a fluid (e.g., gas or liquid) to move in and out ofthe fluid tight volume 1644 to inflate and deflate the balloon 1634.

The catheter 1682 includes a surface 1624 defining a guide-wire lumen1626 that extends through and/or along the elongate body 1602. Asillustrated, the guide-wire lumen 1626 is concentric relative to thelongitudinal center axis 1608. As discussed herein, the guide-wire lumen1626 could also be eccentric relative to longitudinal center axis 1608of the elongate body 1608. Such embodiments are discussed herein, wherethe guide-wire lumen 1626 can have a wall thickness takenperpendicularly to the longitudinal center axis 1608 that is greaterthan a wall thickness of a remainder of the catheter 1682 takenperpendicularly to the longitudinal center axis 1608. The catheter 1682can also include a serpentine portion of the elongate body 1602 proximalto the one or more electrodes 1614.

The elongate body 1602 of the catheter 1684 further includes a surface1686 defining an electrode lumen 1688. The electrode lumen 1688 includesa first opening 1690 and a second opening 1692 in the elongate body1602. The catheter 1684 also includes an elongate electrode member 1694,where the elongate electrode member 1694 retractably extends through thefirst opening 1690 of the electrode lumen 1688 of the elongate body1602. The electrode lumen 1688 has a size (e.g., a diameter) sufficientto allow the elongate electrode member 1694 to pass through theelectrode lumen 1688 to that the elongate electrode member 1694 canretractably extend through the first opening 1690 of the electrode lumen1688 of the elongate body 1602. The elongate electrode member 1694 canretractably extend through the first opening 1690 of the electrode lumen1688 of the elongate body 1602 from pressure (e.g., compression ortension) applied by the user (e.g., clinician or professional) throughthe elongate electrode member 1694 proximal to the second opening 1692in the elongate body 1608. For the various embodiments, the elongateelectrode member 1694 is formed of a flexible polymeric material.Examples of such flexible polymeric material include, but are notlimited to, those flexible materials described herein.

The elongate electrode member 1694 includes one or more electrodes 1696and conductive elements 1698 extending through the electrode lumen 1688.As illustrated, the one or more electrodes 1696 are on the surface 1601of the elongate electrode member 1694. Conductive elements 1698 extendthrough the elongate electrode member 1694, where the conductiveelements 1698 can be used, such as discussed herein, to conductelectrical current to combinations of the one or more electrodes 1696.Each of the one or more electrodes 1696 is coupled to a correspondingconductive element 1698.

The conductive elements 1698 may be electrically isolated from eachother and extend through the elongate electrode member 1694 from eachrespective electrode 1696 through the second end 1692 of the electrodelumen 1688. The conductive elements 1698 terminate at a connector port,where each of the conductive elements 1698 can be releasably coupled toa stimulation system, as discussed herein. It is also possible that theconductive elements 1698 are permanently coupled to the stimulationsystem (e.g., not releasably coupled). The stimulation system can beused to conduct electrical current or electrical pulses to combinationsof the one or more electrodes 1694 via the conductive elements 1698. Theone or more electrodes 1696 are electrically isolated from one another,where the elongate electrode member 1694 is formed of an electricallyinsulating material.

The number and the configuration of the one or more electrodes 1696 onthe elongate electrode member 1694 can vary in different embodiments.For example, as illustrated, the one or more electrodes 1696 can beconfigured as an array of electrodes, where the number of electrodes andtheir relative position to each other can vary depending upon thedesired implant location. As discussed herein, the one or moreelectrodes 1696 can be configured to allow for electrical current to bedelivered from and/or between different combinations of the one or moreelectrodes 1696. So, for example, the electrodes in the array ofelectrodes can have a repeating pattern where the electrodes are equallyspaced from each other. Other patterns are possible, where such patternscan either be repeating patterns or random patterns.

As illustrated, the one or more electrodes 1696 have an exposed face1603. The exposed face 1603 of the electrode 1696 provides theopportunity for the electrode 1696, when implanted (temporarily or foran extended duration of time) in the patient, to be placed intoproximity and/or in contact with the vascular tissue of the patient, asopposed to facing into the volume of blood in the artery. To accomplishthis, the one or more electrodes 1696 can be located on only one side ofthe elongate electrode member 1694 (as illustrated in FIG. 16 ). Thisallows the one or more electrodes 1696 to be brought into contact withthe vascular luminal surface (e.g., a posterior surface of the mainpulmonary artery and/or one or both of the pulmonary arteries). As theone or more electrodes 1696 are located on only one side of the elongateelectrode member 1694, the electrodes 1696 can be placed into directproximity to and/or in contact with the tissue of any combination of themain pulmonary artery, the left pulmonary artery and/or the rightpulmonary artery.

The exposed face 1603 of the one or more electrodes 1696 can have avariety of shapes, as discussed herein (e.g., a partial ringconfiguration, where each of the one or more electrodes 1696 ispositioned to face away from the elongate body 1602). The exposed face1603 of the electrodes 1696 can also include one or more anchorstructures. Examples of such anchor structures include hooks that canoptionally include a barb.

As generally illustrated, the elongate electrode member 1694 can beadvanced through the electrode lumen 1688 so that the elongate electrodemember 1694 extends laterally away from the elongate body 1608. Theelongate electrode member 1694 can be of a length and shape that allowsthe elongate electrode member 1694 to be extended a distance sufficientfrom the elongate body 1608 to bring the one or more electrodes 1696into contact with the vascular luminal surface (e.g., a posteriorsurface of the main pulmonary artery and/or one or both of the pulmonaryarteries).

As illustrated in FIG. 16 , the elongate electrode member 1694 forms aloop 1605 that extends away from the peripheral surface 1636 of theelongate body 1602. The loop 1605 can have a variety of configurationsrelative the longitudinal axis 1608 of the elongate body 1602. Forexample, as illustrated in FIG. 16 , the elongate electrode member 1692forming the loop 1605 is in a plane 1607 that is co-linear with thelongitudinal center axis 1608 of the elongate body 1602.

The catheter 1684 further includes an elongate deflection member 1660,as previously discussed. As discussed herein, pressure is applied to thedeflection member 1660 to move the first end 1663 of the deflectionmember 1660 towards the first opening 1656 of the deflection lumen 1654.The pressure, in addition to moving the first end 1663 of the deflectionmember 1660 towards the first opening 1656, also causes the second end1665 of the deflection member 1660 to extend from the second opening1658. As generally illustrated, the elongate deflection member 1660 canbe advanced through the deflection lumen 1654 so that elongatedeflection member 1660 extends laterally away from the one or moreelectrodes 1696 on the elongate electrode member 1694. The elongatedeflection member 1660 can be of a length and shape that allows theelongate deflection member 1660 to be extended a distance sufficient tohelp bring the one or more electrodes 1696 into contact with thevascular luminal surface (e.g., a posterior surface of the mainpulmonary artery and/or one or both of the pulmonary arteries) with avariety of pressures. Optionally, the elongate deflection member 1660can be configured to include one or more of the electrodes.

The catheter 1684 shown in FIG. 16 can be positioned in the mainpulmonary artery and/or one or both of the left and right pulmonaryarteries of the patient, such as described herein. To accomplish this, apulmonary artery guide catheter is introduced into the vasculaturethrough a percutaneous incision and guided to the right ventricle (e.g.,using a Swan-Ganz catheterization approach). For example, the pulmonaryartery guide catheter can be inserted into the vasculature via aperipheral vein of the arm, neck or chest (e.g., as with a peripherallyinserted central catheter). Changes in a patient's electrocardiographyand/or pressure signals from the vasculature can be used to guide andlocate the pulmonary artery guide catheter within the patient's heart.Once in the proper location, a guide wire can be introduced into thepatient via the pulmonary artery guide catheter, where the guide wire isadvanced into the main pulmonary artery and/or one of the pulmonaryarteries. Using the guide-wire lumen 1626, the catheter 1684 can beadvanced over the guide wire so as to position the catheter 1684 in themain pulmonary artery and/or one or both of the right and left pulmonaryarteries of the patient. Various imaging modalities can be used inpositioning the guide wire of the present disclosure in the mainpulmonary artery and/or one of the right and left pulmonary arteries ofthe patient. Such imaging modalities include, but are not limited to,fluoroscopy, ultrasound, electromagnetic, and electropotentialmodalities.

Using a stimulation system, such as the stimulation systems discussedherein, stimulation electrical energy (e.g., electrical current orelectrical pulses) can be delivered across combinations of one or moreof the electrodes 1696. It is possible for the patient's cardiacresponse to the stimulation electrical energy to be monitored andrecorded for comparison to other subsequent tests. It is appreciatedthat for any of the catheters discussed herein any combination ofelectrodes, including reference electrodes (as discussed herein)positioned within or on the patient's body, can be used in providingstimulation to and sensing cardiac signals from the patient.

Referring now to FIG. 17 , there is shown an additional embodiment of acatheter 1784. The catheter 1784 can include the features and componentsof the catheters described above in connection with FIGS. 12A-12D, 14A,14B, 15A, 15B and/or 16 , a discussion of which is not repeated but theelement numbers are included in FIG. 17 with the understanding that thediscussion of these elements is implicit. The catheter 1784 illustratesan embodiment in which the elongate electrode member 1794 forms a loop1705 in a plane 1707 that is perpendicular to the longitudinal centeraxis of the elongate body. More than one of the elongate electrodemembers can be used with a catheter, in accordance with severalembodiments.

Referring now to FIGS. 18A through 18C, there are shown perspectiveviews of an example catheter 1830 that is suitable for performingcertain methods of the present disclosure. The catheter 1830 includes anelongate catheter body 1832 having a proximal or first end 1834 and adistal or second end 1836. The elongate catheter body 1832 also includesan outer or peripheral surface 1838 and an interior surface 1840defining a lumen 1842 (shown with a broken line) that extends betweenthe first end 1834 and the second end 1836 of the elongate catheter body1832.

The catheter 1830 further includes a plurality of electrodes 1844positioned along the peripheral surface 1838 of the elongate catheterbody 1832. In some embodiments, the electrodes 1844 are proximate to adistal end 1836 of the catheter 1830. Conductive elements 1846 extendthrough and/or along the elongate body 1832, where the conductiveelements 1846 can be used, as discussed herein, to conduct electricalpulses to combinations of the plurality of electrodes 1844. Each of theplurality of electrodes 1844 is coupled (e.g., electrically coupled) toa corresponding conductive element 1846. The conductive elements 1846are electrically isolated from each other and extend through theelongate body 1832 from each respective electrode 1844 through the firstend 1834 of the elongate body 1832. The conductive elements 1846terminate at a connector port, where each of the conductive elements1846 can be releasably coupled to a stimulation system. It is alsopossible that the conductive elements 1846 are permanently coupled tothe stimulation system (e.g., not releasably coupled). As discussed morefully herein, the stimulation system can be used to provide stimulationelectrical pulses that are conducted through the conductive elements1846 and delivered across combinations of the plurality of electrodes1844. Other positions and configurations of electrodes are alsopossible. PCT Patent App. Nos. PCT/US2015/031960, PCT/US2015/047770, andPCT/US2015/047780 are incorporated herein by reference in theirentirety, and more specifically the electrodes (e.g., electrodes ondeployable filaments) and electrode matrices disclosed therein areincorporated herein by reference.

The elongate body 1832 may comprise (e.g., be at least partially formedof) an electrically insulating material. Examples of such insulatingmaterial can include, but are not limited to, medical gradepolyurethanes, such as polyester-based polyurethanes, polyether-basedpolyurethanes, and polycarbonate-based polyurethanes; polyamides,polyamide block copolymers, polyolefins such as polyethylene (e.g., highdensity polyethylene); and polyimides, among others.

The catheter 1830 optionally includes an anchor 1848. The anchor 1848includes struts 1850 that form an open framework, where the struts 1850extend laterally or radially outwardly from the elongate body 1832(e.g., from a peripheral surface 1838 of the elongate body 1832) to atleast partially define a peripheral surface 1852 configured to engagevascular tissue (e.g., configured to appose sidewalls forming the lumenof the right pulmonary artery and/or the left pulmonary artery). FIGS.18A through 18C show the anchor 1848 positioned between the second end1836 and the plurality of electrodes 1844 of the elongate catheter body1832. It is also possible that the anchor 1848 can be positioned betweenthe plurality of electrodes 1844 and the second end 1836 of the elongatecatheter body 1832. In some embodiments, the anchor 1848 can inhibit orprevent at least a portion of the catheter 1830 (e.g., the portion 1854,a portion comprising the electrodes 1844) from extending intovasculature smaller than the expanded struts 1850. For example, withreference to FIG. 19 , the plurality of electrodes 1944 can be proximalto the branch point 1976 such that portions of the catheter 1930proximal to the anchor 1948 do not extend into the two additionalarteries 1978. If the sensor 1966 is distal to the anchor 1948,interaction of the anchor 1948 and the branch point 1976 may ensure thatthe sensor 1966 is in a pulmonary artery branch vessel 1978.

The struts 1850 can have a cross-sectional shape and dimension thatallow for the struts 1850 to provide a radial force sufficient to holdthe catheter 1830 at the implant location within the pulmonary arteryunder a variety of situations, as discussed herein. The struts 1850 canbe formed of a variety of materials, such as a metal, metal alloy,polymer, etc. Examples of such metals or metal alloys include surgicalgrade stainless steel, such as austenitic 316 stainless among others,and the nickel and titanium alloy known as Nitinol. Other metals and/ormetal alloys, as are known or may be developed, can be used.

A portion 1854 of the elongate catheter body 1832, for example thatincludes one, some, none, or all the plurality of electrodes 1844, cancurve in a predefined radial direction (e.g., anterior, posterior,inferior, superior, and combinations thereof), for example when placedunder longitudinal compression. To provide the curve in the portion1854, the elongate catheter body 1832 can be pre-stressed and/or thewall can have thicknesses that allow for the elongate catheter body 1832to curve in the predefined radial direction, for example when placedunder longitudinal compression. In addition, or alternatively,structures such as coils or a helix of wire having different turns perunit length, a hypotube having varying kerf spacing, etc. can be locatedin, around, and/or along the elongate catheter body 1832 in the portion1854. One or more of these structures can be used to allow thelongitudinal compression to create the curve in the predefined radialdirection in the portion 1854. To achieve the longitudinal compression,the anchor 1848 can be deployed in the vasculature of the patient (e.g.,in the pulmonary artery), where the anchor 1848 provides a location orpoint of resistance against the longitudinal movement of the elongatebody 1832. As such, this allows a compressive force to be generated inthe elongate catheter body 1832 sufficient to cause the portion 1854 ofthe elongate catheter body 1832, for example along which the pluralityof electrodes 1844 are present, to curve in the predefined radialdirection.

FIG. 18D provides an illustration of the portion 1854 of the elongatecatheter body 1832 curved in a predefined radial direction when placedunder longitudinal compression. The catheter 1830 illustrated in FIG.18D is similar to the catheter 1830 shown in FIG. 18A and is describedherein, although other catheters having similar features can also beused. In the catheter 1830 illustrated in FIG. 18D, a sensor 1866 isproximal to the electrodes 1844. When the electrodes 1844 are in theright pulmonary artery 206, the sensor 1866 can be in the pulmonarytrunk 202, for example. If the sensor 1866 is more proximal, the sensor1866 can be in the right ventricle, the superior vena cava, etc.Positioning the sensor 1866 proximal along the catheter 1830 can allowthe sensor 1866 to be in a location different than the location of theelectrode 1844 without positioning the sensor 1866 separate frompositioning the electrode 1844. As illustrated in FIG. 18D, the catheter1830 has been at least partially positioned within the main pulmonaryartery 202 of a patient's heart 200, where the anchor 1848 is located inthe lumen of the right pulmonary artery 206. From this position, alongitudinal compressive force applied to the elongate catheter body1832 can cause the portion 1854 of the elongate catheter body 1832,along with at least some of the plurality of electrodes 1844 in thisembodiment, to curve in the predefined radial direction, superior inthis embodiment. The curvature allows (e.g., causes) the plurality ofelectrodes 1844 to extend towards and/or touch the luminal surface ofthe main pulmonary artery 202 and/or right pulmonary artery 206.Preferably, the plurality of electrodes 1844 are brought into positionand/or contact with the luminal surface of the main pulmonary artery 202and/or right pulmonary artery 206.

In some embodiments, the elongate catheter body 1832 of the catheter1830 can use the lumen 1842 that extends from the first end 1834 towardsthe second end 1836 to provide a curve in a predefined radial direction.For example, the catheter 1830 can include a shaping wire 1857 having afirst end 1859 and a second end 1861, as illustrated in FIG. 18A. Theshaping wire 1857 can be bent and retain a desired shape that, uponinsertion into the lumen 1842, can at least partially provide thecatheter 1830 with a curve. The lumen 1842 has a size (e.g., a diameter)sufficient to allow the shaping wire 1857 to pass through the lumen 1842with the second end 1861 of the shaping wire 1857 proximate to thesecond end 1836 of the elongate catheter body 1832 so that the bentportion 1863 of the shaping wire 1857 imparts a curve into the portion1854 of the elongate catheter body 1832, allowing the plurality ofelectrodes 1844 to extend towards and/or touch the luminal surface ofthe main pulmonary artery. In some embodiments the shaping wire 1857 cancomplement the portion 1854. In some embodiments, the shaping wire 1857can be used in place of the portion 1854 (e.g., if the catheter 1830does not include the portion 1854 or by not imparting the longitudinalcompressive force). In some embodiments, the shaping wire 1857 can beused to impart a curve that is contrary to the curve that the portion1854 would cause if a compressive force was applied. In someembodiments, the shaping wire 1857 may be inserted into the lumen 1842in any rotational orientation such that a curve can be imparted in anydesired radial direction, for example depending on the position of theanchor 1848. The shaping wire 1857 can allow formation of a curve evenif the catheter 1830 does not include an anchor 1848, for examplebecause the catheter body 1832 can conform to the shape of the shapingwire regardless of whether the catheter 1830 is anchored to thevasculature. In some embodiments, insertion of the shaping wire 1857into the lumen 1842 imparts a curve to the portion 1854 such that atleast one of the electrodes 1844 apposes a superior/posterior sidewallof the pulmonary artery.

In some embodiments, a neuromodulation system comprises a catheter 1830and a shaping wire 1857. The catheter 1830 comprises a catheter body1832, an electrode 1844, and a sensor 1866. The catheter body 1832comprises a proximal end 1834, a distal end 1836, a lumen 1842 extendingfrom the proximal end 1834 towards the distal end 1836 (e.g., at leastdistal to the electrode 1844), and an outer surface 1838. The electrode1844 is on the outer surface 1838. The electrode 1844 is configured todeliver an electrical signal to a pulmonary artery of a patient (e.g.,to provide calibration and/or therapeutic stimulation to a nerveproximate the pulmonary artery).

The shaping wire 1857 comprises a material that is configured to causethe catheter body 1832 to bend. For example, the radial force of theshaping wire 1857 may be greater than the forces that keep the catheterbody 1832 in a generally straight configuration. In some embodiments,the shaping wire 1857 comprises a shape memory material (e.g., nitinol,chromium cobalt, copper aluminum nickel, etc.) or a resilient material(e.g., stainless steel, etc.). For example, the shaping wire 1857 may bestressed to a straight wire in a proximal portion of the catheter 1830,but in a portion of the catheter 1830 to be bent, which may be, forexample, weaker that the proximal portion of the catheter 1830, theshaping wire 1857 can revert to the unstressed curved shape within thecatheter 1830. In some embodiments in which the shaping wire 1857comprises a shape memory material, the shaping wire 1857 may utilizethermal shape memory. For example, the shaping wire 1857 may be in asubstantially straight shape until cold or warm fluid (e.g., saline)causes reversion to the curved shape. In some such embodiments, theentire catheter 1830 may be bendable by the shaping wire 1857, but thetemperature change is effected once the shaping wire 1857 is in adesired longitudinal and/or radial position. In some embodiments, theentire catheter 1830 may be bendable by the shaping wire 1857. Forexample, the curve may propagate along the length of the catheter 1830until the curve is in a desired position.

The shaping wire 1857 has a diameter or cross-sectional dimension lessthan the diameter or cross-sectional dimension of the lumen 1842. Forexample, if the catheter body 1832 is 20 French (Fr) (approx. 6.67millimeters (mm)), the lumen 1842 may be 18 Fr (approx. 6 mm) and theshaping wire 1857 may be 16 Fr (approx. 5.33 mm). The shaping wire 1857may be, for example 1 Fr less than the lumen 1842 (e.g., for more radialforce than if 2 Fr less) or 2 Fr less than the lumen 1842 (e.g., forless friction during navigation than if 1 Fr less). The shaping wire1857 may be, for example 2 Fr less than the catheter body 1832 (e.g., ifthe lumen 1842 is 1 Fr less than the catheter body 1832) or 4 Fr lessthan the catheter body 1832 (e.g., providing flexibility for the size ofthe lumen 1842 to be 1 or 2 Fr less than the catheter body). Shapingwire sizes other than on a French catheter scale are also possible(e.g., having a diameter less than a diameter of the lumen 1842 by about0.05 mm, 0.1 mm, by about 0.2 mm, by about 0.25 mm, by about 0.5 mm,ranges between such values etc.).

The sensor 1866 is on the outer surface 1838. The sensor 1866 isconfigured to sense a heart activity property (e.g., a non-electricalheart activity property such as a pressure property, an accelerationproperty, an acoustic property, a temperature, and a blood chemistryproperty) from a location within in vasculature of the patient. Thelocation may be different than the pulmonary artery in which theelectrode 1844 is positioned. For example, if the electrode 1844 is inthe right pulmonary artery, the location of the sensor 1866 may be inthe pulmonary trunk, a pulmonary artery branch vessel, the rightventricle, the ventricular septal wall, the right atrium, the septalwall of the right atrium, the superior vena cava, the inferior venacava, the left pulmonary artery, the coronary sinus, etc. The shapingwire 1857 is configured to be positioned in the lumen 1842 of thecatheter body 1832. The shaping wire comprising a bent portion 1863. Forexample, from a proximal end 1859 to a distal end 1861, the shaping wire1857 may be substantially straight in a substantially straight portion,then have a bent portion 1863 extending away from a longitudinal axis ofthe straight portion. The bent portion 1863 may include one bend or aplurality of bends (e.g., two bends (as illustrated in FIG. 18A), threebends, or more bends). The shaping wire 1857 may optionally compriseanother substantially straight portion after the bent portion, which mayhave a longitudinal axis that is substantially aligned with thelongitudinal axis of the proximal straight portion. When the shapingwire 1857 is inserted in the lumen 1842 of the catheter body 1832, thecatheter body 1832 comprises a curved portion 1854 corresponding to thebent portion 1863 of the shaping wire 1857. For example, the catheterbody 1832, or the portion 1854, may comprise a material that can be bentdue to pressure or stress applied to the lumen 1842 or interior surface1840 of the catheter body 1832. In some embodiments, insertion of theshaping wire 1857 into the lumen 1842 imparts a curve to the portion1854 such that at least one of the electrodes 1844 apposes asuperior/posterior sidewall of the pulmonary artery.

FIGS. 18A through 18C further illustrate an example delivery catheter1856 that can be used in conjunction with the catheter 1830. Thedelivery catheter 1856 can be a Swan-Ganz type pulmonary arterycatheter, as are known, that includes a surface 1858 defining a lumen1860 sized sufficiently to receive, store, and deploy the catheter 1830.As illustrated, the delivery catheter 1856 includes a reversiblyinflatable balloon 1862 in fluid communication with a balloon inflationlumen that extends from a proximal or first end 1864 of the deliverycatheter 1856 (e.g., where the inflation lumen can be to an inflationfluid source) to the interior volume of the reversibly inflatableballoon 1862.

The catheter 1830 also includes a first sensor 1866. As illustrated inFIGS. 18A through 18C, the first sensor 1866 can be positioned at anumber of different locations along the catheter 1830. In FIG. 18A, thefirst sensor 1866 is positioned on the elongate catheter body 1832distal to the anchor 1848. A sensor 1866 that is proximate to the distalend 1836 of the catheter 1830 may also or alternatively be useful fornavigation of the catheter 1830, for example to determine an anatomicallocation during floating a balloon such as with a Swan-Ganz catheter. InFIG. 18B, the first sensor 1866 is positioned on or between one of thestruts 1850 of the anchor. In FIG. 18C, the first sensor 1866 ispositioned proximal to both the anchor 1848 and the plurality ofelectrodes 1844. In FIG. 18D, the first sensor 1866 is positionedproximal enough that the first sensor 1866 can be in a location of thevasculature different than the electrodes 1844. In some embodiments, thecatheter 1830 comprises a plurality of sensors 1866 at more than one ofthe positions illustrated in FIGS. 18A through 18C and/or otherpositions.

The catheter 1830 further includes a sensor conductor 1868. The firstsensor 1866 is coupled to the sensor conductor 1868 and is isolated fromthe conductive elements 1846 and electrodes 1844. The coupling may beelectrical, optical, pressure, etc. The sensor conductor 1868 extendsthrough the elongate body 1832 from the first sensor 1866 through thefirst end 1834 of the elongate body 1832. The sensor conductor 1868terminates at a connector port that can be used, for example, toreleasably couple the first sensor 1866 to the stimulation system, asdiscussed herein.

The first sensor 1866 can be used to sense one or more activity property(e.g., electrical and/or non-electrical heart activity properties). Insome embodiments, the property can be measured in response to one ormore electrical pulses delivered using the plurality of electrodes 1844.Examples of non-electrical heart activity properties include, but arenot limited to, one or more of a pressure property, an accelerationproperty, an acoustic property, a temperature, and a blood chemistryproperty measured from within the vasculature of the heart. Asappreciated, two or more of the non-electrical heart activity propertiescan be measured by using more than one sensor on the catheter 1830.

For use in detecting a pressure property, the first sensor 1866 can be apressure sensing transducer, for example such as disclosed in U.S. Pat.No. 5,564,434 (e.g., configured to detect changes in blood pressure,atmospheric pressure, and/or blood temperature and to provide modulatedpressure and/or temperature related signals), incorporated by referenceherein in its entirety. For use in detecting an acceleration property,the first sensor 1866 can be an acceleration sensor, for example such asdisclosed in U.S. Patent Pub. No. 2004/0172079 to Chinchoy (e.g.,configured to generate a signal proportional to acceleration of a heartmuscle or wall such as a coronary sinus wall, septal wall, or ventriclewall) or U.S. Pat. No. 7,092,759 to Nehls et al. (e.g., configured togenerate a signal proportional to acceleration, velocity, and/ordisplacement of a heart muscle or wall such as a coronary sinus wall,septal wall, or ventricle wall), each of which is incorporated byreference herein in its entirety. For use in detecting an acousticproperty, the first sensor 1866 can be a piezoelectric transducer (e.g.,a microphone) or a blood flow sensor, for example such as disclosed inU.S. Pat. No. 6,754,532 (e.g., configured to measure a velocity of bloodto estimate blood flow volume), which is incorporated by referenceherein in its entirety. For use in detecting a temperature, the firstsensor 1866 can be a temperature sensor, for example such as disclosedin U.S. Pat. No. 5,336,244 (e.g., configured to detect variations inblood temperature and/or oxygen concentration indicative of themechanical pumping action of the heart) and/or U.S. Patent Pub. No.2011/0160790 (e.g., configured to sense temperature and to produce atemperature signal), each of which is incorporated by reference hereinin its entirety. For use in detecting a blood chemistry properties, thefirst sensor 1866 can be an oxygen sensor or a glucose sensor, forexample such as disclosed in U.S. Pat. No. 5,213,098 (e.g., configuredto sense blood oxygen saturation levels that vary with cardiac muscleoxygen uptake) and/or U.S. Patent Pub. No. 2011/0160790 (e.g.,configured to measure oxygen and/or glucose concentration in blood andto produce an oxygen and/or glucose signal), each of which isincorporated by reference herein in its entirety. Other types of sensorscan also be used for the first sensor 1866, other sensors describedherein, and the like.

The catheter 1830 shown in FIGS. 18A through 18C can be positioned inthe right pulmonary artery, the left pulmonary artery, or the pulmonarytrunk of the patient, for example as described herein. To accomplishthis, the delivery catheter 1856 with the catheter 1830 housed thereincan be introduced into the vasculature through a percutaneous incision,and guided to the right ventricle. For example, the delivery catheter1856 can be inserted into the vasculature via a peripheral vein of theneck or chest (e.g., as with a Swan-Ganz catheter). Changes in apatient's electrocardiography and/or pressure signals from thevasculature can be used to guide and locate the pulmonary arterycatheter within the patient's heart. Once in the proper location, aguide wire can be introduced into the patient via the pulmonary arteryguide catheter, where the guide wire is advanced into the desiredpulmonary artery (e.g., the right pulmonary artery). The deliverycatheter 1856 with the catheter 1830 housed therein can be advanced overthe guide wire so as to position the catheter 1830 in the desiredpulmonary artery of the patient (e.g., the right pulmonary artery or theleft pulmonary artery), for example as described herein. Various imagingmodalities can be used in positioning the guide wire of the presentdisclosure in the pulmonary artery of the patient. Such imagingmodalities include, but are not limited to, fluoroscopy, ultrasound,electromagnetic, and electropotential modalities.

When the catheter 1830 is positioned in the right pulmonary artery orthe left pulmonary artery and the sensor 1866 is configured to beproximal to the electrodes 1844, a distance between the electrodes 1844(e.g., from the proximal-most electrode 1844) and the sensor 1866 may bebetween about 1 cm and about 5 cm (e.g., about 1 cm, about 2 cm, about 3cm, about 4 cm, about 5 cm, ranges between such values, etc.), in whichcase the sensor 1866 can reside in the pulmonary trunk, between about 8cm and about 20 cm (e.g., about 8 cm, about 9 cm, about 10 cm, about 11cm, about 12 cm, about 13 cm, about 14 cm, about 16 cm, about 18 cm,about 20 cm, ranges between such values, etc.), in which case the sensor1866 can reside in the right ventricle, between about 16 cm and about 27cm (e.g., about 16 cm, about 17 cm, about 18 cm, about 19 cm, about 20cm, about 21 cm, about 22 cm, about 23 cm, about 25 cm, about 27 cm,ranges between such values, etc.), in which case the sensor 1866 canreside in the right atrium, or between about 21 cm and about 33 cm(e.g., about 21 cm, about 23 cm, about 25 cm, about 26 cm, about 27 cm,about 28 cm, about 29 cm, about 30 cm, about 31 cm, about 32 cm, about33 cm, ranges between such values, etc.), in which case the sensor 1866can reside in the superior vena cava.

When the catheter 1830 is positioned in the pulmonary trunk and thesensor 1866 is configured to be distal to the electrodes 1844, adistance between the electrodes 1844 (e.g., from the distal-mostelectrode 1844) and the sensor 1866 may be between about 1 cm and about5 cm (e.g., about 1 cm, about 2 cm, about 3 cm, about 4 cm, about 5 cm,ranges between such values, etc.), in which case the sensor 1866 canreside in the right pulmonary artery or the left pulmonary artery. Whenthe catheter 1830 is positioned in the pulmonary trunk and the sensor1866 is configured to be proximal to the electrodes 1844, a distancebetween the electrodes 1844 (e.g., from the proximal-most electrode1844) and the sensor 1866 may be between about 3 cm and about 19 cm(e.g., about 3 cm, about 5 cm, about 6 cm, about 7 cm, about 8 cm, about9 cm, about 10 cm, about 12 cm, about 15 cm, about 19 cm, ranges betweensuch values, etc.), in which case the sensor 1866 can reside in theright ventricle, between about 11 cm and about 26 cm (e.g., about 11 cm,about 13 cm, about 15 cm, about 16 cm, about 17 cm, about 18 cm, about19 cm, about 20 cm, about 22 cm, about 24 cm, about 26 cm, rangesbetween such values, etc.), in which case the sensor 1866 can reside inthe right atrium, or between about 16 cm and about 32 cm (e.g., about 16cm, about 18 cm, about 20 cm, about 22 cm, about 24 cm, about 25 cm,about 26 cm, about 27 cm, about 28 cm, about 30 cm, about 32 cm, rangesbetween such values, etc.), in which case the sensor 1866 can reside inthe superior vena cava.

FIG. 19 provides a perspective view of a catheter 1930 positioned in theheart 200 of a subject (e.g., patient), where one or more of a pluralityof electrodes 1944 are contacting the posterior 221 and/or superiorsurface 223 of the right pulmonary artery 206 (e.g., at a position thatis superior to the branch point 207). FIG. 19 further illustrates theembodiment in which the first sensor 1966 is positioned distal from theanchor 1948. As illustrated, the pulmonary trunk 202 has a diameter 1970taken across a plane 1972 substantially perpendicular to both the leftlateral plane 220 and the right lateral plane 216.

In a preferred embodiment, the plurality of electrodes 1944 of thecatheter 1930 is positioned in an area 1974 that extends distally nomore than about three times the diameter 1970 of the pulmonary trunk 202to the right of the branch point 207. This area 1974 is shown withcross-hatching in FIG. 19 .

The right pulmonary artery 206 can also include a branch point 1976 thatdivides the right pulmonary artery 206 into at least two additionalarteries 1978 that are distal to the branch point 207 defining the leftpulmonary artery 208 and the right pulmonary artery 206. As illustratedin FIG. 19 , the plurality of electrodes 1944 can be positioned betweenthe branch point 207 defining the left pulmonary artery 208 and theright pulmonary artery 206 and the branch point 1976 that divides theright pulmonary artery 206 into at least two additional arteries 1978.In other words, the plurality of electrodes 1944 of the catheter 1930could be positioned so as to contact the posterior 221 and/or superiorsurface 223 of the right pulmonary artery 206 up to an including thebranch point 1976.

Once positioned in a pulmonary artery of the heart of the patient (e.g.,the right pulmonary artery 206 as illustrated in FIG. 19 , the leftpulmonary artery 208, and/or the pulmonary trunk 202), one or moretherapeutic and/or calibrating electrical pulses can be deliveredthrough the plurality of electrodes 1944 of the catheter 1930. One ormore heart activity properties in response to the one or more electricalpulses are sensed from at least the first sensor 1966 positioned at afirst location within the vasculature of the heart 200.

The catheter 1830, 1930 may be permanently or reversibly implantableinto the vasculature. For example, the catheter 1830, 1930 may beretracted from the vasculature (e.g., after removing the anchor 1848,1948) after a duration. The duration may be determined based at leastpartially on a set duration (e.g., a certain number of hours or days(e.g., 12 hours, 18 hours, 24 hours, 2 days, 3 days, 4 days, 5 days, 6days, etc.)). The duration may be determined based at least partially ona response of a patient (e.g., retracted when the patient has improvedin an aspect by a certain amount or is deemed ready to have the catheter1830, 1930 removed).

FIG. 20 illustrates an example catheter 2030 and a separate first sensor2066 useful for the methods of the present disclosure. Similar to thecatheter 1830, the catheter 2030 includes an elongate catheter body 2032having a proximal or first end 2034 and a distal or second end 2036, aperipheral surface 2038 and an interior surface 2040 defining a lumen2042 (shown with a broken line) that extends between the first end 2034and the second end 2036 of the elongate catheter body 2032. The catheter2030 further includes a plurality of electrodes 2044 positioned alongthe peripheral surface 2038 of the elongate catheter body 2032, andconductive elements 2046 extending through the elongate body 2032between the plurality of electrodes 2044 and the first end 2034, asdiscussed herein. The catheter 2030 further includes an anchor 2048comprising struts 2050 that provide a peripheral surface 2052 that canengage vascular tissue (e.g., the lumen of either the right pulmonaryartery or the left pulmonary artery).

The catheter 2030 further includes a portion 2054 of the elongatecatheter body 2032, for example including the plurality of electrodes2044, where the portion 2054 can curve in a predefined radial directionwhen placed under longitudinal compression, as discussed herein. Theelongate catheter body 2032 of the catheter 2030 can also oralternatively include a lumen 2042 that can receive a shaping wire, asdiscussed herein.

In contrast to the catheter illustrated in FIGS. 18A through 18D,however, the catheter 2030 does not include a first sensor. Rather, asecond catheter 2080 includes a first sensor 2066. As illustrated inFIG. 20 , the second catheter 2080 includes an elongate catheter body2082 having a first end 2084 and a second end 2086, a peripheral surface2088 and an interior surface 2090 defining a lumen 2092 (shown with abroken line) that extends between the first end 2084 and the second end2086 of the elongate catheter body 2082, where the lumen 2092 canreceive a guide wire for help in positioning the second catheter 2080 inthe vasculature of the heart. The second catheter 2080 further includesa first sensor 2066, as discussed herein, on the elongate catheter body2082 and a sensor conductor 2068 that extends through the elongatecatheter body 2082 to terminate at a connector port that can be used,for example, to releasably couple the first sensor 2066 to thestimulation system, as discussed herein.

As the first sensor 2066 is included on the second catheter 2080, thefirst sensor 2066 can be positioned in a location within the vasculatureof the patient that is different than the first location in which thecatheter 2030 is positioned. For example, the catheter 2030 can bepositioned with the plurality of electrodes 2044 positioned in the rightpulmonary artery, as discussed herein, while the first sensor 2066 ispositioned in the left pulmonary artery. In this way, one or moreelectrical pulses can be delivered through the catheter 2030 positionedin the right pulmonary artery of the heart that does not contain thefirst sensor 2066. In some embodiments, when the catheter 2030 ispositioned with the plurality of electrodes 2044 positioned in the leftpulmonary artery, the first sensor 2066 can be positioned in the rightpulmonary artery. In this way, one or more electrical pulses can bedelivered through the catheter 2030 positioned in the left pulmonaryartery of the heart that does not contain the first sensor 2066.

In some embodiments, the catheter 2030 can be positioned with theplurality of electrodes 2044 positioned in either one of the leftpulmonary artery or the right pulmonary artery, and the first sensor2066 on the second catheter 2080 can be positioned in the rightventricle of the heart. The first sensor 2066 on the second catheter2080 can also be positioned in the right atrium of the heart.

In some embodiments, the first sensor 2066 on the second catheter 2080can also be positioned on the septal wall of the right atrium or theventricular septal wall of the heart. The elongate catheter body 2082 ofthe second catheter 2080 can include a positive fixation structure(e.g., a helical screw) that helps to secure the elongate catheter body2082 and the first sensor 2066 to the septal wall of the right atrium ofthe heart.

In some embodiments the first sensor 2066 on the second catheter 2080can be positioned in a superior vena cava of the heart. In someembodiments, the first sensor 2066 on the second catheter 2080 can bepositioned in an inferior vena cava of the heart. In some embodiments,the first sensor 2066 on the second catheter 2080 can be positioned in acoronary sinus of the heart. In a preferred embodiment, when the firstsensor 2066 is positioned in the coronary sinus of the heart, the firstsensor 2066 is used to sense at least one of a temperature and a bloodoxygen level.

One or more cardiac properties can also or alternatively be sensed froma skin surface of the patient. An example of such a cardiac propertyincludes an electrocardiogram property, where the electrical activity ofthe heart can be sensed using electrodes, as are known, attached to thesurface of the patient's skin. Another example of such a cardiacproperty can include a Doppler echocardiogram, which can be used todetermine the speed and direction of the blood flow. Acoustic signalssensed from the skin surface of the patient may also be used as thecardiac property. The properties of the one or more electrical pulsesdelivered through the catheter positioned in the pulmonary artery of theheart can then be adjusted, as discussed herein, in response to the oneor more heart activity properties measured intravascularly and/or theone or more cardiac properties from the skin surface of the patient.

In some embodiments, a second sensor located at a second location withinthe vasculature of the heart can be used, in addition to the firstsensor, to sense one or more heart activity properties, as discussedherein, for example in response to the one or more electrical pulses.The second location is different than the first location. For example,the first location may be the left pulmonary artery and the secondlocation may be the right pulmonary artery; the first location may bethe left pulmonary artery and the second location may be the pulmonarytrunk; the first location may be the left pulmonary artery and thesecond location may be the right ventricle; the first location may bethe left pulmonary artery and the second location may be the rightatrium; the first location may be the left pulmonary artery and thesecond location may be the septal wall of the right atrium; the firstlocation may be the left pulmonary artery and the second location may bethe ventricular septal wall; the first location may be the leftpulmonary artery and the second location may be the superior vena cava;the first location may be the left pulmonary artery and the secondlocation may be the inferior vena cava; the first location may be theleft pulmonary artery and the second location may be the coronary sinus;and other permutations of these locations.

In some embodiments, the second sensor is the sensor 2066 of the secondcatheter 2080, and the first sensor is the sensor 266 of the catheter230. In some embodiments the first sensor and the second sensor can belocated on the same catheter (e.g., the catheter 230, the catheter2080). For example, both the first sensor and the second sensor can belocated on the second catheter 2080 for sensing at least two differentheart activity properties. For another example, both the first sensorand the second sensor can be located on the catheter 230 for sensing atleast two different heart activity properties. The properties of the oneor more electrical pulses delivered through the catheter positioned inthe pulmonary artery of the heart can be adjusted, as discussed herein,in response to the one or more heart activity properties received fromthe first sensor and the second sensor.

Neuromodulation of the heart according to the present disclosure can beaccomplished by applying electrical pulses in and/or around the regionof the pulmonary artery. For example, the neuromodulation of the presentdisclosure can apply the electrical pulses to the posterior, superiorwall, and/or the inferior wall of the right pulmonary artery.Preferably, neuromodulation of the present disclosure includes applyingthe electrical pulses to the posterior and/or superior wall of the rightpulmonary artery, although other positions in the right pulmonaryartery, the left pulmonary artery, and the pulmonary trunk are alsopossible. The electrical pulses are thereby applied to the autonomiccardiopulmonary nerves surrounding the right pulmonary artery. Theseautonomic cardiopulmonary nerves can include the right autonomiccardiopulmonary nerves and the left autonomic cardiopulmonary nerves.The right autonomic cardiopulmonary nerves include the right dorsalmedial cardiopulmonary nerve and the right dorsal lateralcardiopulmonary nerve. The left autonomic cardiopulmonary nerves includethe left ventral cardiopulmonary nerve, the left dorsal medialcardiopulmonary nerve, the left dorsal lateral cardiopulmonary nerve,and the left stellate cardiopulmonary nerve. Stimulation of other nervesproximate to the right pulmonary artery is also possible.

With reference to FIG. 19 , one or more of the plurality of electrodes1944 of the catheter 1930 can be contacting the posterior surface 221 ofthe right pulmonary artery 206. From this location, the electricalpulses delivered through one or more of the plurality of electrodes 1944may be better able to treat and/or provide therapy (including adjuvanttherapy) to the patient experiencing a variety of cardiovascular medicalconditions, such as acute heart failure. The electrical pulses canelicit responses from the autonomic nervous system that may help tomodulate a patient's cardiac contractility. The electrical pulsesapplied by the methods described herein preferably affect heartcontractility more than the heart rate, which can help to improvehemodynamic control while possibly and/or reducing or minimizingunwanted systemic effects.

In accordance with several embodiments, a stimulation system iselectrically coupled to the plurality of electrodes of the cathetersdescribed herein (e.g., via the conductive elements extending throughthe catheter). The stimulation system can be used to deliver thestimulation energy (e.g., electrical current or electrical pulses) tothe autonomic cardiopulmonary fibers surrounding a pulmonary artery(e.g., the right or left pulmonary artery or the main pulmonary arteryor trunk). The stimulation system is used to operate and supply thestimulation energy (e.g., electrical current or electrical pulses) tothe plurality of electrodes of the catheter. The stimulation systemcontrols the various properties of the stimulation energy (e.g.,electrical current or electrical pulses) delivered across the pluralityof electrodes. Such properties include control of polarity (e.g., usedas a cathode or an anode), pulsing mode (e.g., unipolar, bi-polar,biphasic, and/or multi-polar), a pulse width, an amplitude, a frequency,a phase, a voltage, a current, a duration, an inter-pulse interval, adwell time, a sequence, a wavelength, and/or a waveform associated withthe stimulation energy (e.g., electrical current or electrical pulses).The stimulation system may operate and supply the stimulation energy(e.g., electrical current or electrical pulses) to differentcombinations and numbers of the one or more electrodes, including one ormore reference electrodes. The stimulation system can be external to thepatient's body or internal to the patient's body. When located outsidethe body, a professional can program the stimulation system and monitorits performance. When located within the patient, the housing of thestimulation system or an electrode incorporated in the housing can beused as a reference electrode for both sensing and unipolar pulsingmode.

Examples of non-electrical heart activity properties include, but arenot limited to, a pressure property, an acceleration property, anacoustic property, a temperature, or a blood chemistry property. Thenon-electrical heart activity properties may be sensed by at least afirst sensor positioned at a first location within the vasculature ofthe heart. In response to the one or more non-electrical heart activityproperties, a property of the one or more electrical pulses deliveredthrough the catheter positioned in the pulmonary artery of the heart canbe adjusted. Examples of such adjustments include, but are not limitedto, changing which electrode or electrodes of the plurality ofelectrodes on the catheter is/are used to deliver one or more electricalpulses. Adjustments can also be made to the properties of the electricalpulses, for example by changing at least one of an electrode polarity, apulsing mode, a pulse width, an amplitude, a frequency, a phase, avoltage, a current, a duration, an inter-pulse interval, a duty cycle, adwell time, a sequence, a wavelength, a waveform, and/or an electrodecombination of the one or more electrical pulses. It is possible toadjust combinations of electrodes used and the properties of theelectrical pulses provided by the electrodes. Adjusting a property ofthe one or more electrical pulses can include moving the catheter toreposition electrodes of the catheter in the pulmonary artery of theheart. Combinations of these adjustments are also possible.

By way of example, the stimulation energy (e.g., electrical current orelectrical pulses) can have a voltage between about 0.1 microvolts (mV)and about 75 volts (V) (e.g., about 0.1 mV, about 0.5 mV, about 1 mV,about 10 mV, about 100 mV or about 0.1 V, about 1 V, about 10 V, about20 V, about 30 V, about 40 V, about 50 V, about 60 V, about 75 V,between 1 V and 50 V, between 0.1V and 10V, ranges between such values,etc.). The stimulation energy (e.g., electrical current or electricalpulses) can also have an amplitude between about 1 milliamps (mA) toabout 40 mA (e.g., about 1 mA, about 2 mA, about 3 mA, about 4 mA, about5 mA, about 10 mA, about 15 mA, about 20 mA, about 25 mA, about 30 mA,about 35 mA, about 40 mA, ranges between such values, etc.). Thestimulation energy (e.g., electrical current or electrical pulses) canbe delivered at a frequency of between 1 Hertz (Hz) and about 100,000 Hzor 100 kilohertz (kHz) (e.g., between 1 Hz and 10 kHz, between 2 Hz and200 Hz, about 1 Hz, about 2 Hz, about 10 Hz, about 25 Hz, about 50 Hz,about 75 Hz, about 100 Hz, about 150 Hz, about 200 Hz, about 250 Hz,about 500 Hz, about 1,000 Hz or 1 kHz, about 10 kHz, ranges between suchvalues, etc.). The electrical pulses can have a pulse width betweenabout 100 microseconds (vs) and about 100 milliseconds (ms) (e.g., about100 μs, about 200 μs, about 500 μs, about 1,000 μs or 1 ms, about 10 ms,about 50 ms, about 100 ms, ranges between such values, etc.). Forvariation of duty cycle, or the duration that the electrical pulses aredelivered versus the duration that electrical pulses are not delivered,the electrical pulses may be delivered for between about 250 ms andabout 1 second (e.g., about 250 ms, about 300 ms, about 350 ms, about400 ms, about 450 ms, about 500 ms, about 550 ms, about 600 ms, about650 ms, about 700 ms, about 750 ms, about 800 ms, about 850 ms, about900 ms, about 950 ms, ranges between such values, etc.), and thereafternot delivered for between about 1 second and about 10 minutes (e.g.,about 1 second, about 5 seconds, about 10 seconds, about 15 seconds,about 30 seconds, about 45 seconds, about 1 minute, about 2 minutes,about 3 minutes, about 5 minutes, about 10 minutes, ranges between suchvalues, etc.). An optimized duty cycle may, for example, reduce responsetime, increase battery life, patient comfort (reduce pain, cough, etc.),etc. The stimulation energy (e.g., electrical current or electricalpulses) can also have a variety of waveforms, such as: square wave,biphasic square wave, sine wave, arbitrary defined waveforms that areelectrically safe, efficacious, and feasible, and combinations thereof.The stimulation energy (e.g., electrical current or electrical pulses)may be applied to multiple target sites via multiple electrodes at leastpartially simultaneously and/or sequentially.

In some embodiments, the waveform of a stimulation signal is a chargebalanced, constant current cathodic first biphasic waveform with a lowimpedance closed switch second phase electrode discharge. Pulse traincharacteristics can include, for example, a pulse amplitude betweenabout 8 mA and about 20 mA, a pulse width between about 2 ms and about 8ms, and a pulse frequency of about 20 Hz. Pulse amplitude and/or pulsewidth may be lower based on certain electrode designs.

The methods of the present disclosure can include assigning a hierarchyof electrode configurations from which to deliver the one or moreelectrical pulses. The hierarchy can include two or more predeterminedpatterns and/or combinations of the plurality of electrodes to use indelivering the one or more electrical pulses. For example, the one ormore electrical pulses can be delivered using the hierarchy of electrodeconfigurations. A heart activity property sensed in response to the oneor more electrical pulses delivered using the hierarchy of electrodeconfigurations can be analyzed. Such an analysis can include, forexample, determining which of the hierarchy of electrode configurationsprovide the highest contractility or relative contractility of thepatient's heart. Based on this analysis, an electrode configuration canbe selected to use for delivering the one or more electrical pulsesthrough the catheter positioned in the pulmonary artery of the patient'sheart.

In some embodiments, a method can include assigning a hierarchy to oneor more properties of the one or more electrical pulses deliveredthrough the catheter positioned in the pulmonary artery of the heart.The hierarchy can include providing an order of which property (e.g.,electrode polarity, pulsing mode, pulse width, amplitude, frequency,phase, voltage, current, duration, inter-pulse interval, duty cycle,dwell time, sequence, wavelength, or waveform of the one or moreelectrical pulses) is to be changed and by how much, and for apredetermined number of electrical pulses delivered to the patient'sheart. The predetermined number of electrical pulses can be, forexample, 10 to 100 electrical pulses at a given property of thehierarchy. The one or more heart activity properties can be recorded forthe predetermined number of the one or more electrical pulses deliveredto the patient's heart for a given property of the one or moreelectrical pulses. The one or more heart activity properties sensed inresponse to the one or more electrical pulses can then be analyzed. Forexample, the recorded properties for each set of predetermined numbersof pulses can be analyzed against other sets of recorded propertiesand/or against predetermined standards for a given heart activityproperties and/or cardiac property (e.g., contractility). Based on thisanalysis, an electrode configuration can be selected to use fordelivering the one or more electrical pulses through the catheterpositioned in the pulmonary artery of the patient's heart. As anon-limiting example, a current of 1 mA can be applied to an electrodefor 50 electrical pulses, followed by the application of a current of 10mA to the electrode for 50 electrical pulses. The responses at 1 mA and10 mA can be compared. If 10 mA works better, a current of 20 mA can beapplied to the electrode for 50 electrical pulses, and the responses at10 mA and 20 mA can be compared. If 10 mA works better, 10 mA may beselected as the current for the method. A wide variety of selectionprocesses may be used, including but not limited to iterative methods(e.g., comprising making comparisons until a limit is found at which adifference is negligible) and brute force methods (e.g., measuringresponses and selecting one magnitude after completion of all responsesor until a certain value is achieved). This can be repeated for one ormore additional properties according to the hierarchy (e.g., currentfollowed by frequency). The selection process may be the same ordifferent for each member of the hierarchy.

In some embodiments, a first electrical signal of a series of electricalsignals is delivered (e.g., via a stimulation system such as thestimulation system 2101) to an electrode in the pulmonary artery (e.g.,the right pulmonary artery, the left pulmonary artery, the pulmonarytrunk). After delivering the first electrical signal, a secondelectrical signal of the series of electrical signals is delivered(e.g., via the stimulation system) to the electrode. The secondelectrical signal differs from the first electrical signal by amagnitude of a first parameter of a plurality of parameters. Forexample, if the first parameter is current, the first electrical signalmay have a voltage such as 1 mA and the second electrical signal mayhave a different voltage such as 2 mA, while each of the otherparameters (e.g., polarity, pulse width, amplitude, frequency, voltage,duration, inter-pulse interval, dwell time, sequence, wavelength,waveform, and/or an electrode combination) are the same.

Sensor data indicative of one or more non-electrical heart activityproperties may be determined in response to delivering the series ofelectrical signals (e.g., via a sensor in the vasculature (e.g., as partof a same catheter that comprises the electrode, as part of a differentcatheter), via a sensor on a skin surface, combinations thereof, and thelike)). Electrical parameters to use for therapeutic modulation may beselected based at least partially on the sensor data. For example, theselected electrical parameters may comprise a selected magnitude of thefirst parameter. A therapeutic neuromodulation signal may be deliveredto the pulmonary artery using selected electrical parameters. Thetherapeutic neuromodulation signal may increase heart contractility(e.g., more than heart rate).

In some embodiments, a first series of electrical signals is delivered(e.g., via a stimulation system such as the stimulation system 501) toan electrode in the pulmonary artery (e.g., the right pulmonary artery,the left pulmonary artery, the pulmonary trunk). The first seriescomprises a first plurality of electrical signals. Each of the firstplurality of electrical signals comprises a plurality of parameters(e.g., polarity, pulsing mode, pulse width, amplitude, frequency, phase,voltage, current, duration, inter-pulse interval, duty cycle, dwelltime, sequence, wavelength, waveform, electrode combination, subsetsthereof, or the like). Each of the first plurality of electrical signalsof the first series only differs from one another by a magnitude of afirst parameter of the plurality of parameters (e.g., one of polarity,pulsing mode, pulse width, amplitude, frequency, phase, voltage,current, duration, inter-pulse interval, duty cycle, dwell time,sequence, wavelength, and waveform changes in each of the firstplurality of electrical signals). For example, if the first parameter iscurrent, the first plurality of electrical signals of the first seriesmay differ by having different currents such as 1 mA, 2 mA, 3 mA, 4 mA,etc., while each of the other parameters (e.g., polarity, pulsing mode,pulse width, amplitude, frequency, phase, voltage, duration, inter-pulseinterval, duty cycle, dwell time, sequence, wavelength, and waveform)are the same.

After the first series of electrical signals is delivered to theelectrode, a second series of electrical signals can be delivered (e.g.,via the stimulation system) to the electrode. The second seriescomprises a second plurality of electrical signals. Each of the secondplurality of electrical signals comprises the plurality of parameters.Each of the second plurality of electrical signals of the second seriesonly differs from one another by a magnitude of a second parameter ofthe plurality of parameters different than the first parameter (e.g., adifferent one of polarity, pulsing mode, pulse width, amplitude,frequency, phase, voltage, current, duration, inter-pulse interval, dutycycle, dwell time, sequence, wavelength, and waveform changes in each ofthe second plurality of electrical signals). For example, if the firstparameter is current, the second parameter may be related to timing suchas frequency or duty cycle. For example, in the case of frequency, thesecond plurality of electrical signals of the second series may differby having different frequencies such as 1 Hz, 2 Hz, 3 Hz, 4 Hz, etc.,while each of the other parameters (e.g., current, polarity, pulsingmode, pulse width, amplitude, phase, voltage, duration, inter-pulseinterval, duty cycle, dwell time, sequence, wavelength, and waveform)are the same.

Sensor data indicative of one or more non-electrical heart activityproperties may be determined in response to delivering the first seriesof electrical signals and the second series of electrical signals (e.g.,via a sensor in the vasculature (e.g., as part of a same catheter thatcomprises the electrode, as part of a different catheter), via a sensoron a skin surface, combinations thereof, and the like)). Electricalparameters to use for therapeutic modulation may be selected based atleast partially on the sensor data. For example, the selected electricalparameters may comprise a selected magnitude of the first parameter anda selected magnitude of the second parameter. A therapeuticneuromodulation signal may be delivered to the pulmonary artery usingselected electrical parameters. The therapeutic neuromodulation signalmay increase heart contractility (e.g., more than heart rate).

Other series of electrical signals may be delivered to the electrode,for example only differing from one another by a magnitude of adifferent parameter of the plurality of parameters than the firstparameter and the second parameter. As many parameters as may be desiredto have a selected value may be calibrated or optimized. An order of theparameters may be based on a hierarchy (e.g., first select a current,then select a frequency, etc.).

A calibration or optimization process may be performed once (e.g., whena catheter 1830, 1930 is initially positioned) or a plurality of times.For example, the process may be repeated periodically or after a certainduration (e.g., once per hour, per 2 hours, per 4 hours, per 6 hours,per 8 hours, per 12 hours, per 18 hours, per 24 hours, per 36 hours, per2 days, per 60 hours, per 3 hours, etc.). In some implementations theprocess may be repeated upon detection of a change (e.g., by the sensor266, 366, 466). For example, if a heart activity property changes bymore than a certain percentage in a certain duration (e.g., ±10%, ±25%,±50%, etc. in <1 minute, <2 minutes, <5 minutes, etc.), that may beindicative that the catheter and/or sensor changed position or thatsomething else in the system or patient may have changed (e.g., patientcondition, physiological status, other therapy regiments, etc.).

For example, FIG. 21 illustrates an embodiment of a stimulation system2101. U.S. Provisional Patent App. No. 62/001,729, filed May 22, 2014,is incorporated herein by reference in its entirety, and morespecifically the stimulation system 11600 disclosed in FIG. 11 and page41, line 5 to page 42, line 19 are incorporated herein by reference. Asshown in FIG. 21 , the stimulation system 2101 includes an input/outputconnector 2103 that can releasably join the conductive elements of thecatheter, conductive elements of a second catheter, and/or sensors forsensing the one or more cardiac properties from the skin surface of thepatient, as discussed herein. An input from the sensor can also bereleasably coupled to the input/output connector 11602 so as to receivethe sensor signal(s) discussed herein. The conductive elements and/orsensors may be permanently coupled to the stimulation system (e.g., notreleasably coupled).

The input/output connector 2103 is connected to an analog to digitalconverter 2105. The output of the analog to digital converter 2105 isconnected to a microprocessor 2107 through a peripheral bus 2109including, for example, address, data, and control lines. Themicroprocessor 2107 can process the sensor data, when present, indifferent ways depending on the type of sensor in use. Themicroprocessor 2107 can also control, as discussed herein, the pulsecontrol output generator 2111 that delivers the stimulation electricalenergy (e.g., electrical pulses) to the one or more electrodes via theinput/output connector 2103 and/or housing 2123.

The parameters of the stimulation electrical energy (e.g., properties ofthe electrical pulses) can be controlled and adjusted, if desired, byinstructions programmed in a memory 2113 and executed by a programmablepulse generator 2115. The memory 2113 may comprise a non-transitorycomputer-readable medium. The memory 2113 may include one or more memorydevices capable of storing data and allowing any storage location to bedirectly accessed by the microprocessor 2107, such as random accessmemory (RAM), flash memory (e.g., non-volatile flash memory), and thelike. The stimulation system 2101 may comprise a storage device, such asone or more hard disk drives or redundant arrays of independent disks(RAID), for storing an operating system and other related software, andfor storing application software programs, which may be the memory 2113or a different memory. The instructions in memory 2113 for theprogrammable pulse generator 2115 can be set and/or modified based oninput from the sensors and the analysis of the one or more heartactivity properties via the microprocessor 2107. The instructions inmemory 2113 for the programmable pulse generator 2115 can also be setand/or modified through inputs from a professional via an input 2117connected through the peripheral bus 2109. Examples of such an inputinclude a keyboard and/or a mouse (e.g., in conjunction with a displayscreen), a touch screen, etc. A wide variety of input/output (I/O)devices may be used with the stimulation system 2101. Input devicesinclude, for example, keyboards, mice, trackpads, trackballs,microphones, and drawing tablets. Output devices include, for example,video displays, speakers, and printers. The I/O devices may becontrolled by an I/O controller. The I/O controller may control one ormore I/O devices. An I/O device may provide storage and/or aninstallation medium for the stimulation system 2101. The stimulationsystem 2101 may provide USB connections to receive handheld USB storagedevices. The stimulation system 2101 optionally includes acommunications port 2119 that connects to the peripheral bus 2109, wheredata and/or programming instructions can be received by themicroprocessor 2107 and/or the memory 2113.

Input from the input 2117 (e.g., from a professional), thecommunications port 2119, and/or from the one or more heart activityproperties via the microprocessor 2107 can be used to change (e.g.,adjust) the parameters of the stimulation electrical energy (e.g.,properties of the electrical pulses). The stimulation system 2101optionally includes a power source 2121. The power source 2121 can be abattery or a power source supplied from an external power supply (e.g.,an AC/DC power converter coupled to an AC source). The stimulationsystem 2101 optionally includes a housing 2123.

The microprocessor 2107 can execute one or more algorithms in order toprovide stimulation. The microprocessor 2107 can also be controlled by aprofessional via the input 2117 to initiate, terminate, and/or change(e.g., adjust) the properties of the electrical pulses. Themicroprocessor 2107 can execute one or more algorithms to conduct theanalysis of the one or more heart activity properties sensed in responseto the one or more electrical pulses delivered using the hierarchy ofelectrode configurations and/or the hierarchy of each property of theone or more electrical pulses, for example to help identify an electrodeconfiguration and/or the property of the one or more electrical pulsesdelivered to the patient's heart. Such analysis and adjustments can bemade using process control logic (e.g., fuzzy logic, negative feedback,etc.) so as to maintain control of the pulse control output generator2111.

In some embodiments, the stimulation is operated with closed loopfeedback control. In some embodiments, input is received from aclosed-looped feedback system via the microprocessor 2107. The closedloop feedback control can be used to help maintain one or more of apatient's cardiac parameters at or within a threshold value or rangeprogrammed into memory 2113. For example, under closed loop feedbackcontrol measured cardiac parameter value(s) can be compared and then itcan be determine whether or not the measured value(s) lies outside athreshold value or a pre-determined range of values. If the measuredcardiac parameter value(s) do not fall outside of the threshold value orthe pre-determined range of values, the closed loop feedback controlcontinues to monitor the cardiac parameter value(s) and repeats thecomparison on a regular interval. If, however, the cardiac parametervalue(s) from a sensor indicate that one or more cardiac parameters areoutside of the threshold value or the pre-determined range of values oneor more of the parameters of the stimulation electrical energy will beadjusted by the microprocessor 2107.

The stimulation system 2101 may comprise one or more additionalcomponents, for example a display device, a cache memory (e.g., incommunication with the microprocessor 2107), logic circuitry, signalfilters, a secondary or backside bus, local buses, local interconnectbuses, and the like. The stimulation system 2101 may support anysuitable installation device, such as a CD-ROM drive, a CD-R/RW drive, aDVD-ROM drive, tape drives of various formats, USB device, hard-drive,communication device to a connect to a server, or any other devicesuitable for installing software and programs. The stimulation system2101 may include a network interface to interface to a Local AreaNetwork (LAN), Wide Area Network (WAN), or the Internet through avariety of connections including, but not limited to, standard telephonelines, LAN or WAN links, broadband connections, wireless connections(e.g., Bluetooth, WiFi), combinations thereof, and the like. The networkinterface may comprise a built-in network adapter, network interfacecard, wireless network adapter, USB network adapter, modem, or any otherdevice suitable for interfacing the stimulation system 2101 to any typeof network capable of communication and performing the operationsdescribed herein. In some embodiments, the stimulation system 2101 maycomprise or be connected to multiple display devices, which may be ofthe same or different in type and/or form. As such, any of the I/Odevices and/or the I/O controller may comprise any type and/or form ofsuitable hardware, software, or combination of hardware and software tosupport, enable, or provide for the connection and use of multipledisplay devices by the stimulation system 2101. The stimulation systemcan interface with any workstation, desktop computer, laptop or notebookcomputer, server, handheld computer, mobile telephone, any othercomputer, or other form of computing or telecommunications device thatis capable of communication and that has sufficient processor power andmemory capacity to perform the operations described herein and/or tocommunication with the stimulation system 2101. The arrows shown in FIG.21 generally depict the flow of current and/or information, but currentand/or information may also flow in the opposite direction depending onthe hardware.

Analysis, determining, adjusting, and the like described herein may beclosed loop control or open loop control. For example, in closed loopcontrol, a stimulation system may analyze a heart activity property andadjust an electrical signal property without input from a user. Foranother example, in open loop control, a stimulation system may analyzea heart activity property and prompt action by a user to adjust anelectrical signal property, for example providing suggested adjustmentsor a number of adjustment options.

In some embodiments, a method of non-therapeutic calibration comprisespositioning an electrode in a pulmonary artery of a heart andpositioning a sensor in a right ventricle of the heart. The systemfurther comprises delivering, via a stimulation system, a first seriesof electrical signals to the electrode. The first series comprises afirst plurality of electrical signals. Each of the first plurality ofelectrical signals comprises a plurality of parameters. Each of thefirst plurality of electrical signals of the first series only differsfrom one another by a magnitude of a first parameter of the plurality ofparameters. The method further comprises, after delivering the firstseries of electrical signals to the electrode, delivering, via thestimulation system, a second series of electrical signals to theelectrode. The second series comprises a second plurality of electricalsignals. Each of the second plurality of electrical signals comprisesthe plurality of parameters. Each of the second plurality of electricalsignals of the second series only differs from one another by amagnitude of a second parameter of the plurality of parameters. Thesecond parameter is different than the first parameter. The methodfurther comprises determining, via the sensor, sensor data indicative ofone or more non-electrical heart activity properties in response todelivering the first series of electrical signals and the second seriesof electrical signals. The method further comprises determining atherapeutic neuromodulation signal to be delivered to the pulmonaryartery using selected electrical parameters. The selected electricalparameters comprise a selected magnitude of the first parameter and aselected magnitude of the second parameter. The selected magnitudes ofthe first and second parameters are based at least partially on thesensor data.

In some embodiments, a method of non-therapeutic calibration comprisesdelivering a first electrical signal of a series of electrical signalsto an electrode in a first anatomical location and, after delivering thefirst electrical signal, delivering a second electrical signal of theseries of electrical signals to the electrode. The second electricalsignal differs from the first electrical signal by a magnitude of afirst parameter of a plurality of parameters. The method furthercomprises sensing, via a sensor in a second anatomical locationdifferent than the first anatomical location, sensor data indicative ofone or more non-electrical heart activity properties in response to thedelivery of the series of electrical signals, and determining atherapeutic neuromodulation signal to be delivered to the firstanatomical location using selected electrical parameters. The selectedelectrical parameters comprise a selected magnitude of the firstparameter. The selected magnitude of the first parameter is based atleast partially on the sensor data.

In some embodiments, the stimulation system can be used to help identifya preferred location for the position of the one or more electrodesalong the posterior, superior and/or inferior surfaces of the mainpulmonary artery, left pulmonary artery, and/or right pulmonary artery.To this end, the one or more electrodes of the catheter or cathetersystem are introduced into the patient and tests of various locationsalong the posterior, superior and/or inferior surfaces of thevasculature using the stimulation system are conducted so as to identifya preferred location for the electrodes. During such a test, thestimulation system can be used to initiate and adjust the parameters ofthe stimulation electrical energy (e.g., electrical current orelectrical pulses). Such parameters include, but are not limited to,terminating, increasing, decreasing, or changing the rate or pattern ofthe stimulation electrical energy (e.g., electrical current orelectrical pulses). The stimulation system can also deliver stimulationelectrical energy (e.g., electrical current or electrical pulses) thatis episodic, continuous, phasic, in clusters, intermittent, upon demandby the patient or medical personnel, or preprogrammed to respond to asignal, or portion of a signal, sensed from the patient.

An open-loop or closed-loop feedback mechanism may be used inconjunction with the present disclosure. For the open-loop feedbackmechanism, a professional can monitor cardiac parameters and changes tothe cardiac parameters of the patient. Based on the cardiac parametersthe professional can adjust the parameters of the electrical currentapplied to autonomic cardiopulmonary fibers. Non-limiting examples ofcardiac parameters monitored include arterial blood pressure, centralvenous pressure, capillary pressure, systolic pressure variation, bloodgases, cardiac output, systemic vascular resistance, pulmonary arterywedge pressure, gas composition of the patient's exhaled breath and/ormixed venous oxygen saturation. Cardiac parameters can be monitored byan electrocardiogram, invasive hemodynamics, an echocardiogram, or bloodpressure measurement or other devices known in the art to measurecardiac function. Other parameters such as body temperature andrespiratory rate can also be monitored and processed as part of thefeedback mechanism.

In a closed-loop feedback mechanism, the cardiac parameters of thepatient are received and processed by the stimulation system, where theparameters of the electrical current are adjusted based at least in parton the cardiac parameters. As discussed herein, a sensor is used todetect a cardiac parameter and generate a sensor signal. The sensorsignal is processed by a sensor signal processor, which provides acontrol signal to a signal generator. The signal generator, in turn, cangenerate a response to the control signal by activating or adjusting oneor more of the parameters of the electrical current applied by thecatheter to the patient. The control signal can initiate, terminate,increase, decrease or change the parameters of the electrical current.It is possible for the one or more electrodes of the catheter to be usedas a sensor a recording electrode. When necessary these sensing orrecording electrodes may deliver stimulation electrical energy (e.g.,electrical current or electrical pulses) as discussed herein.

The stimulation system can also monitor to determine if the one or moreelectrodes have dislodged from their position within the right pulmonaryartery. For example, impedance values can be used to determine whetherthe one or more electrodes have dislodged from their position within theright pulmonary artery. If changes in the impedance values indicate thatthe one or more electrodes have dislodged from their position within theright pulmonary artery, a warning signal is produced by the stimulationsystem and the electrical current is stopped.

In several embodiments, the catheters provided herein include aplurality of electrodes, which includes two or more electrodes. It isunderstood that the phrase “a plurality of electrodes” can be replacedherein with two or more electrodes if desired. For the variousembodiments of catheters and systems disclosed herein, the electrodescan have a variety of configurations and sizes. For example, theelectrodes discussed herein can be ring-electrodes that fully encirclethe body on which they are located. The electrodes discussed herein canalso be a partial ring, where the electrode only partially encircles thebody on which they are located. For example, the electrodes can bepartial ring electrodes that preferably only contact the luminal surfaceof the main pulmonary artery and/or pulmonary arteries, as discussedherein. This configuration may help to localize the stimulationelectrical energy, as discussed herein, into the vascular and adjacenttissue structures (e.g., autonomic fibers) and away from the blood. Theelectrodes and conductive elements provided herein can be formed of aconductive biocompatible metal or metal alloy. Examples of suchconductive biocompatible metal or metal alloys include, but are notlimited to, titanium, platinum or alloys thereof. Other biocompatiblemetal or metal alloys are known.

For the various embodiments, the elongate body of the catheters providedherein can be formed of a flexible polymeric material. Examples of suchflexible polymeric material include, but are not limited to, medicalgrade polyurethanes, such as polyester-based polyurethanes,polyether-based polyurethanes, and polycarbonate-based polyurethanes;polyamides, polyamide block copolymers, polyolefins such as polyethylene(e.g., high density polyethylene); and polyimides, among others.

Each of the catheters and/or catheter systems discussed herein canfurther include one or more reference electrodes positioned proximal tothe one or more electrodes present on the elongate body. These one ormore reference electrodes can each include insulated conductive leadsthat extend from the catheter and/or catheter system so as to allow theone or more reference electrodes to be used as common or returnelectrodes for electrical current that is delivered through one or moreof the one or more electrodes on the elongate body of the catheterand/or catheter system.

With respect to treating cardiovascular medical conditions, such medicalconditions can involve medical conditions related to the components ofthe cardiovascular system such as, for example, the heart and aorta.Non-limiting examples of cardiovascular conditions includepost-infarction rehabilitation, shock (hypovolemic, septic, neurogenic),valvular disease, heart failure including acute heart failure, angina,microvascular ischemia, myocardial contractility disorder,cardiomyopathy, hypertension including pulmonary hypertension andsystemic hypertension, orthopnea, dyspenea, orthostatic hypotension,dysautonomia, syncope, vasovagal reflex, carotid sinus hypersensitivity,pericardial effusion, and cardiac structural abnormalities such asseptal defects and wall aneurysms.

In some embodiments, a catheter, for example as discussed herein, can beused in conjunction with a pulmonary artery catheter, such as aSwan-Ganz type pulmonary artery catheter, to deliver transvascularneuromodulation via the pulmonary artery to an autonomic target site totreat a cardiovascular condition. In certain such embodiments, thecatheter (or catheters) is housed within one of the multiple lumens of apulmonary artery catheter.

In addition to the catheter and catheter system of the presentdisclosure, one or more sensing electrodes can be located on or withinthe patent. Among other things, the sensing electrodes can be used todetect signals indicting changes in various cardiac parameters, wherethese changes can be the result of the pulse of stimulation electricalenergy delivered to stimulate the nerve fibers (e.g., autonomic nervefibers) surrounding the main pulmonary artery and/or one or both of thepulmonary arteries. Such parameters include, but are not limited to, thepatient's heart rate (e.g., pulse), among other parameters. The sensingelectrodes can also provide signals indicting changes in one or moreelectrical parameter of vasculature (electrical activity of the cardiaccycle). Such signals can be collected and displayed, as are known, usingknown devices (e.g., electrocardiography (ECG) monitor) or a stimulationsystem, as discussed herein, which receives the detected signals andprovides information about the patient.

Other sensors can also be used with the patient to detect and measure avariety of other signals indicting changes in various cardiacparameters. Such parameters can include, but are not limited to, bloodpressure, blood oxygen level and/or gas composition of the patient'sexhaled breath. For example, catheter and catheter system of the presentdisclosure can further include a pressure sensor positioned within orin-line with the inflation lumen for the inflatable balloon. Signalsfrom the pressure sensor can be used to both detect and measure theblood pressure of the patient. Alternatively, the catheter and cathetersystem of the present disclosure can include an integrated circuit forsensing and measuring blood pressure and/or a blood oxygen level. Suchan integrated circuit can be implemented using 0.18 μm CMOS technology.The oxygen sensor can be measured with optical or electrochemicaltechniques as are known. Examples of such oxygen sensors includereflectance or transmissive pulse oximetry those that use changes inabsorbance in measured wavelengths optical sensor to help determined ablood oxygen level. For these various embodiments, the elongate body ofthe catheter can include the sensor (e.g., a blood oxygen sensor and/ora pressure sensor) and a conductive element, or elements, extendingthrough each of the elongate body, where the conductive element conductselectrical signals from the blood oxygen sensor and/or the pressuresensor.

The detected signals can also be used by the stimulation system toprovide stimulation electrical energy in response to the detectedsignals. For example, one or more of these signals can be used by thestimulation system to deliver the stimulation electrical energy to theone or more electrodes of the catheter or catheter system. So, forexample, detected signals from the patent's cardiac cycle (e.g., ECGwaves, wave segments, wave intervals or complexes of the ECG waves) canbe sensed using the sensing electrodes and/or timing parameter of thesubject's blood pressure. The stimulation system can receive thesedetected signals and based on the features of the signal(s) generate anddeliver the stimulation electrical energy to the one or more electrodeof the catheter or catheter system. As discussed herein, the stimulationelectrical energy is of sufficient current and potential along with asufficient duration to stimulate one or more of the nerve fiberssurrounding the main pulmonary artery and/or one or both of thepulmonary arteries so as to provide neuromodulation to the patient.

FIG. 22A is a perspective view of an example of a portion 2200 of acatheter. FIG. 22B is a side elevational view of the portion 2200 ofFIG. 22A. FIG. 22C is a distal end view of the portion 2200 of FIG. 22A.FIG. 22D is a proximal end view of the portion 2200 of FIG. 22A. Theportion 2200 may be coupled to or form part of a catheter (e.g., anall-in-one catheter or a telescoping catheter), for example as describedherein.

The portion 2200 comprises a first cut hypotube 2202 and a second cuthypotube 2204 coupled at points 2206. As may be appropriate for any ofthe cut hypotubes described herein, a sheet may be cut and rolled into ahypotube with an intermediate shape setting into a tube or directly intoa final shape. The first cut hypotube 2202 comprises a cylindrical(e.g., uncut) portion 2208 and a plurality of splines 2210. The secondcut hypotube 2204 comprises a cylindrical (e.g., uncut) portion 2212 anda plurality of splines 2214. As may be best seen in FIG. 22B, thesplines 2210 are convex and the splines 2214 are concave.

In the embodiment illustrated in FIGS. 22A and 22B, the distal ends ofthe splines 2210 are coupled radially inward of, but proximate to, thedistal ends of the splines 2214 at the points 2206. In some embodiments,the distal ends of the splines 2210 may be coupled to the splines 2214even further radially inward. In some embodiments, the distal ends ofthe splines 2214 may be coupled radially inward of the distal ends ofthe splines 2210. The points 2206 may be proximate to the distal ends ofthe splines 2210 and the distal ends of the splines 2214 (e.g., as shownin FIGS. 22A and 22B), between the distal ends of the splines 2214 andpoints along the splines 2210 (e.g., an approximate longitudinalmidpoint, about 75% of the length closer to the distal end, etc.), orbetween the distal ends of the splines 2210 and points along the splines2214 (e.g., including embodiments in which the splines 2214 areconfigured to be convex distal to the points 2206).

As shown in FIGS. 22C and 22D, the cylindrical portion 2212 telescopesradially inward of the cylindrical portion 2208. The cylindrical portion2212 has a lower diameter than the cylindrical portion 2208. As thecylindrical portion 2208 and the cylindrical portion 2212 moverelatively away from each other (e.g., by distal advancement of thesecond cut hypotube 2204 and/or proximal retraction of the first cuthypotube 2202), the splines 2204 push the splines 2210 radially outward.

FIGS. 22A-22D illustrate six splines 2210 and six splines 2214. Othernumbers of splines 2210, 2214 are also possible (e.g., between 2 and 12(e.g., about 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, ranges between suchvalues, etc.)). The splines 2210, 2214 may be uniformlycircumferentially spaced, or some splines 2210, 2214 may be closercircumferentially. The splines 2210, 2214 may provide a circumferentialcoverage between about 60° and 360° (e.g., about 60°, about 90°, about120°, about 180°, about 210°, about 240°, about 270°, about 300°, 360°,ranges between such values, etc.). If the portion 2200 is rotatable tofind a target nerve, the circumferential coverage may optionally be atthe lower end of the range. As described with respect to FIG. 22E, atleast some of the splines 2210 may comprise electrodes. Others of thesplines 2210 may be free of electrodes or include electrodes that arenot used, but may act as apposition arms (e.g., in cases when thesplines 2210 are not pushed to a side of a vessel due to rigidity and anatural course of a navigation path), which can help push the electrodesagainst or close to the tissue.

FIGS. 22E-22G are side partial cross-sectional views of an example of acatheter 2220 including the portion 2200 of FIG. 22A. The splines 2210comprise electrodes 2222, for example on an exterior surface, annularlyaround, in U-shaped channels (e.g., as described herein), as part of amesh covering (e.g., as described with respect to FIG. 4C), etc. In someembodiments, the length 2223 of the parts of the splines 2210 comprisingelectrodes is between about 20 mm and about 40 mm (e.g., about 20 mm,about 25 mm, about 30 mm, about 35 mm, about 40 mm, ranges between suchvalues, etc.). The first cut hypotube 2202 is coupled to a cannula orsheath 2226. The first cut hypotube 2202 may be coupled in a lumen ofthe cannula 2226 (e.g., as shown in FIGS. 22E and 22G), on an outside ofthe cannula 2226, end-to-end, by tethers, etc. The cannula 2226 may havea diameter between about 7 Fr and about 11 Fr (e.g., about 7 Fr, about 8Fr, about 9 Fr, about 10 Fr, about 11 Fr, ranges between such values,etc.). The second cut hypotube 2204 is coupled to an inner member 2224.The second cut hypotube 2204 may be coupled in a lumen of the innermember 2224 (e.g., as shown in FIG. 22G), on an outside of the innermember 2224, end-to-end, by tethers, etc. FIG. 22G shows the first cuthypotube 2202 in cross-section to show the coupling between the secondcut hypotube 2204 and the inner member 2224. Relative movement betweenthe inner member 2224 (and thus the second cut hypotube 2204) and thecannula 2226 (and thus the first cut hypotube 2202) can cause thesplines 2210 to flex radially (e.g., proximal retraction of the cannula2226 and/or distal advancement of the inner member 2224 can cause thesplines 2210 to flex radially outward, proximal retraction of the innermember 2210 and/or distal advancement of the cannula 2226 can cause thesplines 2210 to flex radially inward), as shown in FIG. 22F. Since thesplines 2214 can push the splines 2210 radially outward, the splines2210 can be free of a taper, which can reduce the profile and length ofthe catheter 2220 and the throw distance. In some embodiments, thediameter 2225 of the splines 2210 in the expanded state is between about15 mm and about 35 mm (e.g., about 15 mm, about 20 mm, about 25 mm,about 30 mm, about 35 mm, ranges between such values, etc.).

A potential advantage of a catheter 2220 in which the splines 2210 arein a collapsed position (FIG. 22F) is that in the event of a failure(e.g., proximal breakage), the splines 2210 collapse inwardly instead ofexpanding. That is, the collapsed state is the default state, which maybe safer than an expanded state being a default state, for example whenthe catheter 2220 passes by valves, chordae tendinae, etc. A potentialadvantage of not using shape memory material, which is possible whenexpansion is due to longitudinal movement, is reduced costs.

In some embodiments, the splines 2210 may be self-expanding, for exampleable to expand upon removal of a force from the inner member 2224.Reduced length can be useful when a target vessel is short, for examplea pulmonary artery. Relative movement may be manual or, for example asdescribed herein, spring assisted.

In some embodiments, the catheter 2220 may comprise a fixation systemseparate from the portion 2200. For example, the fixation system mayextend through the lumen of the second cut hypotube 2204. The fixationsystem may be axially and rotationally movable relative to the portion2200, which can be useful to provide appropriate fixation and nervetargeting. Once a user is satisfied with the positions of the portion2200 and the fixation system, the portion 2200 and the fixation systemmay be coupled (e.g., at a handle outside the subject). Even oncecoupled, the portion 2200 and the fixation system may be able to rotate(e.g., ±20°) and/or move longitudinally, (e.g., ±1 cm, ±2 cm) relativeto each other. The portion 2200 may be moved to improve nerve targetingeven while the fixation mechanism does not move, which can reduce tissuedisturbance. In some embodiments, distal ends of the splines 2214 mayprovide alternate or additional fixation.

In some embodiments, the splines 2210, the splines 2204, or another partof the portion 2200 or the catheter 2220 comprises a sensor (e.g., apressure sensor, a contractility sensor, etc.).

In some embodiments, rotation of a proximal handle may impartlongitudinal movement and/or rotational movement that is not 1:1 at thedistal end of the catheter 2220, for example due to catheter shape,bending, or other factors.

FIGS. 22H-22L are side elevational and partial cross-sectional views ofexamples of catheter deployment systems 2230, 2240. In FIGS. 22H-22J,the proximal end or handle of the catheter deployment systems areillustrated. In FIGS. 22K and 22L, the proximal end or handle of thecatheter deployment systems are illustrated. The catheter deploymentsystems 2230, 2240 may be used, for example, with the catheter 2220.

The system 2230 comprises a spring 2232. The spring abuts a gripper2234, which is coupled to the inner member 2224. The spring 2232 has anegative spring constant (restoring force is inwards), but a springhaving a positive spring constant (restoring force outwards) is alsopossible by rearrangement of other features. To expand the splines 2210,a handle element 2236 such as a knob is pushed distally relative to thecannula 2226, against the force of the spring 2232. The system 2230 maycomprise a locking mechanism 2238 configured to hold the handle element2236 in a distal position. In the system 2230, in the event of a breakin the system 2230 (e.g., failure of the locking mechanism 2238), thespring 2232 retracts the inner element 2224, collapsing the splines2210, which can allow for easy recovery of the catheter 2220. The spring2232 may provide a range of deployment options compared to a solelymanual structure, for example due to forces provided by the spring 2232.

FIG. 22I shows an example of the locking mechanism 2238 comprising aplurality of arms that can resiliently hold the handle element 2236 in adistal position. The arms may be open at a proximal end, and the handleelement 2236 (e.g., the entire handle element 2236) may be captured inthe arms. When the splines 2210 are to be collapsed, the arms may beopened, allowing the spring 2232 to force the handle element 2236proximally, retracting the inner element 2224 and collapsing the splines2210.

FIG. 22J shows another example of the locking mechanism 2238 comprisinga plurality of arms that can resiliently hold the handle element 2236 ina distal position. The arms may be closed at a proximal end. The armsmay be biased radially outward to promote radial expansion. The arms mayact as secondary leaf springs. In some embodiments, the handle element2236 and the closed proximal end of the locking mechanism 2238 compriseVelcro®, magnets, threads, or other features to hold the handle element2236 in a distal position. When the splines 2210 are to be collapsed,the handle element 2236 may be disengaged, allowing the spring 2232 (andthe arms) to force the handle element 2236 proximally, retracting theinner element 2224 and collapsing the splines 2210. In some embodiments,compressing the arms can cause the handle element 2236 to be disengaged.

The system 2240 comprises a spring 2242. The spring abuts a gripper2244, which is coupled to the inner member 2224. The spring 2242 has apositive spring constant (restoring force is inwards), but a springhaving a positive spring constant (restoring force outwards) is alsopossible by rearrangement of other features.

In FIG. 22K, to expand the splines 2210, a handle element coupled to theinner member 2224 is pulled proximally relative to the cannula 2226,against the force of the spring 2242. The pulling element 2246 iscoupled to the inner member 2224. The pulling element 2246 is coupled tosplines 2247 (e.g., similar to the splines 2214 but opposite inorientation such that the splines 2247 extend distally in a collapsedstate). As the pulling element 2246 is pulled proximally, the splines2247 expand radially outward, pushing the splines 2210 radially outwardto an expanded state.

In FIG. 22L, the splines 2210 have a slightly tapered shapes so that apulling element 2246 can rest between the splines 2210 in a collapsedstate and interact with the splines 2210 during retraction. To expandthe splines 2210, a handle element coupled to the inner member 2224 ispulled proximally relative to the cannula 2226, against the force of thespring 2242. The pulling element 2246 is coupled to the inner member2224. As the pulling element 2246 is pulled proximally, the proximal endof the pulling element 2246 bears against the inside surfaces of thesplines 2210, pushing the splines 2210 radially outward to an expandedstate.

In the system 2240 of FIGS. 22K and 22L, in the event of a break in thesystem 2240, the spring 2242 advances the inner element 2224, collapsingthe splines 2210, which can allow for easy recovery of the catheter2220. The spring 2242 may provide a range of deployment options comparedto a solely manual structure, for example due to forces provided by thespring 2242.

FIG. 22M illustrates an example part 2250 of the portion 2200 of FIG.22A. Rather than a first cut hypotube 2202, the part 2250 comprises ahypotube 2252 coupled to a plurality of wires 2254 shaped into splines2210. The orange wires 2254 o show the shapes of the splines 2210 in anopen or expanded state, and the grey wires 2254 g show the shapes of thesplines 2210 in a closed or collapsed state. As with the splines 2210 ofthe first cut hypotube 2202, the wires 2254 may comprise shape memorymaterial (e.g., nitinol) and/or may be moved to an expanded position bya second cut hypotube 2204 or similar device. Referring to FIGS. 22E and4C, the part 2250 may comprise electrodes on the wires 2254, on a meshattached to the wires 2254, combinations thereof, and the like.

FIG. 23A is a perspective view of an example segment 2300 of a strut.The segment 2300 generally has a U-shape. The segment 2300 compriseswalls 2302 at least partially defining a channel or trough 2304. Thewalls 2302 and trough 2304 may be formed in a variety of ways. In someembodiments, a wire may be extruded in the U-shape. In some embodiments,a hypotube may be cut to form generally rectangular struts, and thetrough 204 may be formed by removing material from the struts (e.g., bymilling). In some embodiments, sides of a flat wire may be bent upwards.In some embodiments, the U-shape may comprise plastic (e.g., extruded,molded, etc.). The trough 2304 may be lined with insulative material. Insome embodiments, the insulative material comprises epoxy. In someembodiments, a trough 2304 lined with insulative material can help tomake electrodes directional, which can help to aim energy at a vesselwall and at a nerve. A plurality of wires or leads or conductors 2306may lie in the trough 2304. Positioning the wires 2306 in the trough2304 can aid in manufacturing (positioning of the wires 2306), mayreduce the risk that the conductors may cross-talk, and/or may protectthe wires 2306 from breaking. The wires 2306 are electrically connectedto electrodes, transducers, and the like that can be used to provideneuromodulation. FIGS. 23B-23F show examples of configurations that maybe used to position wires 2306, insulator, and an electrode 2308 atleast partially in a U-shaped segment of a strut. In some embodiments, aU-shaped segment may be coupled to a strut (e.g., adhered, welded,soldered, interference fit, etc.).

The trough 2304 may have a depth 2370 between about 0.003 inches andabout 0.02 inches (e.g., about 0.003 inches, about 0.005 inches, about0.01 inches, about 0.015 inches, about 0.02 inches, ranges between suchvalues, and the like). The trough 2306 may have a width 2372 betweenabout 0.15 inches and about 0.1 inches (e.g., about 0.015 inches, about0.02 inches, about 0.025 inches, about 0.05 inches, about 0.06 inches,about 0.08 inches, about 0.1 inches, ranges between such values, and thelike).

FIG. 23B is a transverse cross-sectional view of an example of a strut2320. The strut 2320 includes walls 2302 at least partially defining atrough. In some embodiments, the walls 2302 form a depth 2370 configuredto at least partially laterally cover an electrode 2308. A plurality ofwires 2306 lies in the trough. The wires 2306 are covered by aninsulating sheet or insert 2310. Each of the wires 2306 may be coatedwith insulative material and/or the insulating sheet 2310 may provideinsulation for the wires 2306. Insulation at welds and at junctionsbetween wires 2306 and electrodes 2308 can inhibit or prevent damagefrom body fluids and corrosion. An electrode 2308 is electricallyconnected to one of the wires 2306 through the insulating sheet 2310.The electrode 2308 illustrated in FIG. 23B has a rectangularcross-section. FIG. 23C illustrates a transverse cross-sectional view ofan example of a strut 2325 in which the electrode 2308 has a roundedcross-section (e.g., shaped as a dome), which can help to reduce edgeeffects and hot spots due to sharp edges. In some embodiments in whichthe electrode 2308 includes sharp edges, insulating material can atleast partially cover the sharp edges, which can help reduce edgeeffects. The electrode 2308 may be sunk in a well of insulative materialsuch that only a top surface is exposed, which can help the electrode2308 to be directional. The electrode 2308, as with all electrodesdescribed herein, may lack sharp edges and/or lack sharp edges that arenot covered with insulative material.

FIG. 23D is a cross-sectional view of another example of a strut 2330.The strut 2330 includes walls 2302 at least partially defining a trough.A plurality of wires 2306 lies in the trough. The wires 2306 are coveredby an insulating layer 2312. The insulating layer 2312 may comprise, forexample, silicone or any suitable insulating, flexible material. Each ofthe wires 2306 may be coated with insulative material and/or theinsulating layer 2312 may provide insulation for the wires 2306. Anelectrode 2308 is electrically connected to one of the wires 2306through the insulating layer 2312. The electrode 2308 may be the sameheight as the insulating layer 2312. The insulating layer 2312 mayinclude dome shapes.

FIG. 23E is a transverse cross-sectional view of yet another example ofa strut 2340. The strut 2340 includes walls 2302 at least partiallydefining a trough. A plurality of wires 2306 lies in the trough. Thewires 2306 are covered by an insulating layer 2314. The insulating layer2314 may comprise, for example, silicone or any suitable insulating,flexible material. Each of the wires 2306 may be coated with insulativematerial and/or the insulating layer 2314 may provide insulation for thewires 2306. An electrode 2308 is electrically connected to one of thewires 2306 through the insulating layer 2314. The electrode 2308 may bethe same height as the insulating layer 2314. The insulating layer 2312may include a generally flat or planar upper surface.

FIG. 23F is a transverse cross-sectional view of still another exampleof a strut 2350. The strut 2350 includes walls 2302 at least partiallydefining a trough. A plurality of wires 2306 lies in the trough. Thewires 2306 are covered by an insulating layer 2316. The insulating layer2316 may comprise, for example, silicone or any suitable insulating,flexible material. Each of the wires 2306 may be coated with insulativematerial and/or the insulating layer 2316 may provide insulation for thewires 2306. An electrode 2308 is electrically connected to one of thewires 2306 through the insulating layer 2316. The insulating layer 2316may include a generally crowned surface. The electrode 2308 may be thesunken into the insulating layer 2316, which can help to reduce edgeeffects. Reducing edge effects can increase uniformity of an electricfield emanating from the electrode 2308. An electrode 2308 that is belowan upper surface of the insulating layer 2316 may be spaced from tissue,which can allow blood flow across the electrode 2308.

The insulating layer 2312, 2314, 2316 may maintain positions of thewires 2306 in the U-shaped trough, for example inhibiting tanglingand/or maintaining a spatial separation. The insulating layer 2312,2314, 2316 may protect the wires 2306, for example from body fluids andexternal forces.

The insulating layer 2312, 2314, 2316 may be deposited over the wires2306 in the trough. The insulating layer 2312, 2314, 2316 may be curedand then ablated (e.g., laser ablated, milled) to allow the positioningof the electrode 2308 and a connector thereto. In some embodiments, aplug (e.g., comprising a material that doesn't stick to the material ofthe insulating layer 2312, 2314, 2316, such as PTFE) may be positionedin the insulating layer 2312, 2314, 2316 and then removed after curingto allow the positioning of the electrode 2308 and a connector thereto.

FIG. 23G is a top partial cross-sectional view of an example segment2360 of a strut. As illustrated, the wires 2306 are spatially separated.In embodiments in which the wires 2306 are not individually insulated,the insulating material can inhibit or prevent electrical communicationbetween the wires 2306. A first wire 2306 a is connected to a firstelectrode 2308 a. A second wire 2306 b is connected to a secondelectrode 2308 b. A third wire 2306 c is connected to a third electrode(not shown).

FIG. 23H illustrates an example of a strut system 2380 comprising aplurality of struts or splines 2382 each having a generally U-shapedtrough. The U-shaped troughs can help to align or maintain the spacingor separation distance between the struts 2382. FIG. 23I shows anexample in which a distance b between a first strut 2382 a and a secondstrut 2382 b is less than a distance a between a third strut 2382 c andthe second strut 2382 b. FIG. 23J shows an example in which a distance2374 between a first strut 2382 a and a second strut 2382 b issubstantially the same as a distance a between a third strut 2382 c andthe second strut 2382 b. In some embodiments, the distance b or 2374between struts or strut-to-strut spacing may be between about 10 mm andabout 15 mm (e.g., about 10 mm, about 11 mm, about 12 mm, about 13 mm,about 14 mm, about 15 mm, ranges between such values, etc.). With theU-shape, the splines 2382 may flex less in a radial configuration than around-wire spline system, which can help to keep spacing between thesplines more consistent, whether the spacing is meant to be consistentor varying. The U-shape may reduce the likelihood that the splines 2382slide relative to each other and that the electrodes 2308 in each of thesplines 2382 slide relative to each other, which can maintain spacing ofthe electrodes.

FIG. 23K illustrates an example of an electrode on wire system 2390.

The system 2390 comprises a wire 2392 and an electrode 2394 over (e.g.,radially outward of, annularly or arcuately around) the wire 2392. Thewire 2392 may comprise a shape memory material (e.g., nitinol). Theelectrode 2394 may comprise, for example, a platinum-iridium electrode.Other materials for the wire 2392 and the electrode 2394 are alsopossible. The system 2390 may comprise an insulator 2396 between thewire 2392 and the electrode 2394. The electrode 2394 may be electricallycoupled to a conductor wire 2398. In some embodiments, a single wire2392 may comprise a plurality of electrodes 2394, for example forming anarray.

FIG. 23L is a cross-sectional view of an electrode 2308 spaced from avessel wall 2397. The blood vessel is spaced from a nerve 2399. Theelectrode 2308 may be positioned as close to the vessel wall 2397 aspossible so that the electrode 2308 is as close to the nerve 2399 aspossible. In some embodiments, the electrode 2308 may be intentionallyspaced from the vessel wall 2397 a distance d, which can allow blood toflow both under and over the electrode 2308, for example as shown by thethick arrows. In some embodiments, the distance d is between about 0.1mm and about 1 mm (e.g., about 0.1 mm, about 0.2 mm, about 0.3 mm, about0.5 mm, about 0.7 mm, about 0.9 mm, about 1 mm, ranges between suchvalues, etc.). Referring again to FIG. 23F, the insulating material2316, for example, may act as a spacer. Allowing blood to flow over theelectrode 2308 may inhibit corrosion of the electrode 2308. Allowingblood to flow over the electrode 2308 may allow blood to contact thevessel wall 2397 in the area of the electrode 2308 such that cells maybe replenished. In some embodiments, the electrode may compriselongitudinal channels, a bumpy surface, etc. to allow blood to flowradially outward of the electrode 2308 but to still be closer to thenerve 2399. In certain such embodiments, surface area of the electrode2308 may be advantageously increased.

FIGS. 23Ni-23Nix illustrate an example method of manufacturingcomponents on a substrate 2301. The substrate 2301 may comprise, forexample, a shape-memory alloy such as nitinol forming a spline of anelectrode system. Flex-circuit processing can be used to patternelectrodes, conductors, insulators, and other components (e.g.,resistors) on a spline. In FIG. 23Ni, an insulating layer 2303comprising insulative material (e.g., oxide, polyimide) is depositedover the substrate 2301. If the substrate 2301 is insulating, the layer2303 may be omitted. As used with respect to FIG. 23Ni-23Nix, the term“over” could mean on or directly on as viewed from a certainorientation, and is not intended to limit intervening layers, and theterm “layer” could mean a plurality of layers (e.g., including adhesivelayers). In FIG. 23Nii, a conductive layer 2305 comprising conductivematerial (e.g., aluminum, copper, doped silicon) is deposited over theinsulating layer 2303. In FIG. 23Niii, the conductive layer 2305 ispatterned into conductor wires 2306 (e.g., using photolithography,lift-off lithography, etc.). In some embodiments, the conductor wires2306 may be formed directly (e.g., using screen printing, inkjetprinting). In FIG. 23Niv, an insulating layer 2307 insulative material(e.g., oxide, polyimide) is deposited over the conductor wires 2306 andthe insulating layer 2303. The insulative material of the insulatinglayers 2303, 2307 may be the same or different. In FIG. 23Nv, a via 2311is formed (e.g., via etching, milling) in the insulating layer 2307,exposing a portion of the middle conductor wire 2306. In FIG. 23Nvi, aconductive layer 2309 comprising conductive material (e.g., aluminum,copper, doped silicon) is formed over the insulating layer 2307 andfilling the via 2311. The conductive material of the conductive layers2305, 2309 may be the same or different. In FIG. 23Nvii, the conductivelayer 2309 is patterned into electrodes 2308. Wet etching, for example,may help to form a domed shape of the electrode 2308. Although notillustrated, vias 2311 may be formed to connect each conductor wire 2306to a different electrode 2308. In FIG. 23Nviii, an insulating layer 2313(e.g., comprising oxide, polyimide) is formed over the electrode 2308and the insulating layer 2307. The insulative material of the insulatinglayers 2303, 2307, 2313 may be the same or different. In FIG. 23Nix, theinsulating layer 2313 has been patterned to reveal the electrode 2308and to form an insulating layer 2316 including a generally crownedsurface. The electrode 2308 being sunken into the insulating layer 2316can help to reduce edge effects, which can increase uniformity of anelectric field emanating from the electrode 2308. The electrode 2308 canalso be spaced from tissue by an upper surface of the insulating layer2316, which can allow blood flow across the electrode 2308. In someembodiments, the insulating layer 2316 may be omitted. In someembodiments, a dual damascene structure can be formed in the insulatinglayer 2307 and the electrode 2308 can be formed in the insulating layer2307, which can be shaped to have a crowned surface. A wide variety oflayers, patterns, and processes can be used to form the describedcomponents and other components. For example, a resistor layer may bepatterned proximate to the substrate 2301, which can provide localizedheating, which can cause a shape-memory substrate to locally deform toan austenitic state.

Although not meant to be limiting, the following electrode dimensionsmay be adequate to generate a hemodynamic response due toneurostimulation. About half of the electrodes can be assumed to contactthe vessel and about half of the electrodes can be assumed to be exposedto low impedance blood flow. Referring again to the elevational view ofFIG. 23G as an example, the length of an electrode 2806 may be betweenabout 1 mm and about 3 mm (e.g., about 1 mm, about 1.5 mm, about 2 mm,about 2.5 mm, about 2 mm, ranges between such values, etc.); the widthof an electrode 2806 may be between about 1 mm and about 4 mm (e.g.,about 1 mm, about 2 mm, about 3 mm, about 4 mm, ranges between suchvalues, etc.); and the spacing between electrodes 2806 may be betweenabout 2 mm and about 8 mm (e.g., about 2 mm, about 3 mm, about 4 mm,about 5 mm, about 6 mm, about 7 mm, about 8 mm, ranges between suchvalues, etc.). The spacing between electrodes may refer to the distancebetween a distal end of a proximal electrode and the proximal end of adistal electrode, the distance between the center of one electrode andthe center of another electrode, and/or the distance betweencircumferentially or laterally spaced electrodes. The electrode 2308 maybe configured to maintain a charge density at an electrochemicallystable level less than about 400 μC/cm² for Pt/Ir^(1,2,3). Referringagain to FIG. 23G as an example of an annular electrode, the electrodes2394 may have a diameter of about 7 Fr (approx. 2.3 mm), have a lengthof about 1.5 mm, and be spaced by about 8 mm. In some embodiments, theelectrodes 2394 may have a length between about 1 mm and about 3 mm(e.g., about 1 mm, about 1.5 mm, about 2 mm, about 2.5 mm, about 2 mm,ranges between such values, etc.), a diameter between about 0.5 mm andabout 1.5 mm (e.g., about 0.5 mm, about 0.75 mm, about 1 mm, about 1.25mm, about 1.5 mm, ranges between such values, etc.), and spacing betweenabout 1 mm and about 3 mm (e.g., about 1 mm, about 1.5 mm, about 2 mm,about 2.5 mm, about 2 mm, ranges between such values, etc.).

The target nerve may be a very small target to capture vianeurostimulation. Electrodes, most likely the cathode, may need to bevery close to the nerve, if not by depth than by lateral positioning.One option to provide close lateral positioning is to have aneffectively infinite number of electrodes, or at least an electrodematrix that can cover all possible areas of the nerve with respect tothe target vessel. Another option to provide close lateral positioningis to provide repositionable electrodes, for example electrodes in amatrix that can be extended, retracted, and/or rotated.

FIG. 23M shows an example electrode matrix. The electrodes are spacededge-to-edge by about 2 mm proximal-distal and superior-inferior. Theinitial target area estimate may be as large as 15 mm superior-inferiorand 19 mm laterally. In some embodiments, for example as illustrated inFIG. 23M, an electrode matrix has these dimensions, which mayeffectively behave as an infinite number of electrodes in view of thesize of the target area. In some embodiments, an electrode matrix mayhave smaller dimensions and may be rotated and/or longitudinally moved.Although illustrated in two dimensions in FIG. 23N, in some embodiments,the electrode matrix may take a three-dimensional shape (e.g.,conforming to an inside wall of a blood vessel). In certain suchembodiments, the electrode matrix may cover between about 15° and about360° of the circumference of the vessel wall (e.g., about 15°, about30°, about 45°, about 60°, about 75°, about 90°, about 105°, about 120°,about 180°, about 210°, about 270°, about 300°, about 360°, rangesbetween such values, etc.). The e values indicate the percent abovebaseline hemodynamic response. The value of e₁ between electrodes C5 andC4 was 3.0%. The value of e₂ between electrodes C4 and C3 was 12.1%. Thevalue of e₃ between electrodes D6 and D5 was 18.5%. The value of e₄between electrodes D5 and D4 was 40.2%. The value of e₅ betweenelectrodes D4 and D3 was 23.7%. The value of e₆ between electrodes E5and E4 was 0%. The value of e₇ between electrodes E5 and E3 was 0.3%.The value of e₈ between electrodes C4 and D4 was 28.9%. The value of e₉between electrodes C3 and D3 was 21.3%. The value of e₁₀ betweenelectrodes C2 and D2 was 7.1%.

Hemodynamic response decreases by approximately half as the excitationis moved from one pair of electrodes to the adjacent space pair. Whencenter-to-center spacing is 3.5 mm, this would suggest that once anoptimum target has been determined, a movement of the electrode matrixon the order of 3.5 mm would significantly decrease the hemodynamicresponse. Certain fixation systems described herein can limit electrodemovement to less than an order of magnitude of this variation (e.g.,about 0.035 mm total electrode migration), over the therapy applicationperiod. In some embodiments, a fixation system can inhibit electrodemigration to be less than about 1 mm, less than about 0.5 mm, less thanabout 0.25 mm, less than about 0.1 mm, less than about 0.075 mm, lessthan about 0.05 mm, less than about 0.035 mm, less than about 0.025 mm,or less than about 0.015 mm, with the lower limit of such “less than”ranges being 0 mm.

In some embodiments, an electrode matrix (e.g., including a portion ofan electrode utilized for calibration stimulation and/or therapeuticstimulation) may have an area between about 10 mm² and about 15 mm²(e.g., about 10 mm², about 11 mm², about 12 mm², about 13 mm², about 14mm², about 15 mm², ranges between such values, etc.). In someembodiments, an electrode matrix may have an area between about 10 mm²and about 300 mm² (e.g., about 10 mm², about 50 mm², about 100 mm²,about 150 mm², about 200 mm², about 250 mm², about 300 mm², rangesbetween such values, etc.).

FIG. 24A illustrates an example of a fixation system 2400. The fixationsystem 2400 comprises a fixation structure 2402 and fixation mechanisms2404. The fixation structure 2402 may comprise, for example, a hypotubethat has been cut and shape set into a plurality of arms, wires thathave been shape set into a plurality of arms, and the like. The arms maybe the same or different (e.g., as illustrated in FIG. 24A, one arm mayflex upward). The fixation mechanisms 2404 may comprise, for example,points or barbs pointing radially outward from the fixation structure2402. The fixation mechanisms 2404 may be integral with the fixationstructure 2402 or coupled to the fixation structure 2402.

FIGS. 24B and 24C illustrate the fixation system 2400 of FIG. 24Ainteracting with a catheter 2406. As the fixation structure 2402 and thecatheter 2406 are moved longitudinally to each other (e.g., retractingthe fixation structure 2402 and/or advancing the catheter 2406), thearms of the fixation structure 2402 move radially inward. The fixationmechanisms 2402 may injure tissue during this interaction. The fixationmechanisms 2402 may catch on the catheter 2406 (e.g., starting at theend of the catheter 2406) and may dig into the catheter 2406 to formtrenches 2408, which may release catheter residue, use more longitudinalinteraction force, etc. In some embodiments, the catheter 2406 mayinclude grooves or channels configured to accommodate the fixationmechanisms, although radial outward force provided by the fixationstructure 2402 may still tissue injury and/or trenches 2408.

FIG. 25A is a perspective view of another example of a fixation system2500. FIG. 25B is a side elevational view of the fixation system 2500 ofFIG. 25A. FIG. 25C is an end view of the fixation system 2500 of FIG.25A. The fixation system 2500 comprises a fixation structure 2502 and afixation mechanism 2504. The fixation structure 2502 may comprise, forexample, a hypotube that has been cut and shape set, a ribbon that hasbeen shape set, and the like. The fixation mechanisms 2504 may comprise,for example, points or barbs pointing radially outwardly in a deployedposition or state and pointing radially inwardly in a constrainedposition or state due to the fixation structure 2502 comprising arotation or twist 2510. The rotation 2510 may be between about 60° andabout 300° (e.g., about 60°, about 90°, about 120°, about 150°, about180° (e.g., as illustrated in FIGS. 25A-25C), about 210°, about 240°,about 270°, about 300°, ranges between such values, and the like). Insome embodiments, the fixation structure 2502 comprises a shape memorymaterial and the rotation 2510 is imparted as at least part of a shapeset. The fixation mechanism 2504 may be integral with the fixationstructure 2502 or coupled to the fixation structure 2502.

FIGS. 25D and 25E illustrate the fixation system 2500 of FIG. 25Ainteracting with a catheter 2506. As the fixation system 2500 is movedlongitudinally relative to the catheter 2506, the fixation structure2502 rotates relative to the longitudinal axis. The fixation mechanism2502, which faces radially inward in the catheter 2506, rotates to faceradially outward upon extension out of the catheter 2506. Conversely,the fixation mechanism 2502, which faces radially outward out of thecatheter 2506, rotates to face radially inward upon retraction into thecatheter 2506. The fixation structure 2502 may be radially outwardlybiased to push against the lumen of the catheter 2506.

FIG. 25F illustrates an example of a catheter 2506 comprising a lumen2512 having a shape configured to accommodate the fixation structure2502 and the fixation mechanism 2504. The lumen 2512 may, for example,comprise a pentagon configured to interact with three sides of arectangular fixation structure 2502 and a pointed fixation mechanism2504 extending from the other side of the fixation structure 2502. Othershapes of the lumen 2512 are also possible. For example, referring againto FIG. 25C, the lumen 2512 may comprise a generally arcuate shapeconfigured to interact with two sides of a rectangular fixationstructure 2502.

FIGS. 25G-25J illustrate an example deployment of the fixation structure2502 and the fixation mechanism 2504 out of the lumen 2512 of thecatheter 2506 of FIG. 25F. As shown in FIG. 25G, as the fixationstructure 2502 and fixation mechanism 2504 is initially deployed out ofthe lumen 2512 of the catheter 2510, with the twist 2510 still in thelumen 2512, the fixation mechanism 2504 faces radially inwardly. Asshown in FIG. 25H, when the twist 2510 is out of the lumen 2512, thefixation mechanism 2504 can start to turn radially outward. FIG. 25Ishows the fixation mechanism 2504 continuing to turn radially outward asthe twist 2510 is further from the lumen 2512, which allows the shape ofthe fixation structure 2502 to rotate. FIG. 25J shows the fixationmechanism 2504 facing radially outward or standing proud. In someembodiments, the fixation structure 2502 and fixation mechanism 2504 maybe deployed out of an end of the catheter 2506. In some embodiments, thefixation structure 2502 and fixation mechanism 2504 may be deployed outof a side of the catheter.

FIG. 26A is a side elevational view of an example of a catheter system2600. The catheter system 2600 comprises a fixation system 2602 and anelectrode system 2604. The fixation system 2602 may comprise radiallyoutwardly extending features, for example as described herein. Theelectrode system 2604 may comprise a scaffold and electrodes, forexample as described herein. In the embodiment illustrated in FIG. 26A,the electrode system 2604 includes tethers 2605, which can help withpositioning in and out of a sheath 2606. The fixation system 2602 isdistal to the electrode system 2604.

FIGS. 26B-26H illustrate an example method of deploying the cathetersystem 2600 of FIG. 26A. This is an example of an over-the-wire orstepwise placement method in which a balloon is used to place aguidewire, which provides a rail to guide components to a targetlocation.

In FIG. 26A, a Swan-Ganz catheter 2612 comprising a distal balloon 2614is floated to a target area. For example, a Swan-Ganz catheter 2612 maybe inserted into an access point of an internal jugular vein (left orright) in an uninflated state, then inflated, after which it can becarried by blood flow to a target site such as a pulmonary artery (left,right, or trunk). In some embodiments, the Swan-Ganz catheter 2612 is a8 Fr Swan-Ganz catheter having a 1.5 cm³ balloon, for example as isavailable from Edwards Lifesciences Corp. In FIG. 26C, a guidewire 2616is routed through a lumen of the Swan-Ganz catheter 2612 until thedistal end of the guidewire 2614 protrudes from the distal end of theSwan-Ganz catheter 2612. In FIG. 26D, the Swan-Ganz catheter 2612 iswithdrawn, leaving the guidewire 2616.

In FIG. 26E, a fixation catheter 2620 including the fixation system 2602at the distal end of a tether 2622 is advanced over the guidewire 2616and the fixation system 2602 is deployed. In some embodiments, thefixation catheter 2620 is 8 Fr or 9 Fr. In FIG. 26F, the guidewire 2616and the fixation catheter 2620 are withdrawn, leaving the fixationsystem 2602 and the tether 2622 in place. In FIG. 26G, the sheath 2606including the electrode system 2604 is advanced over the tether 2622. Insome embodiments, the distance between the fixation system 2602 and thedistal end of the sheath 2606 may be known, for example, from proximalmarkings. In FIG. 26H, the sheath 2606 is proximally retracted to deploythe electrode system 2604. In some embodiments, the electrode system2604 has a diameter of about 25 mm in the expanded state. The fixationsystem 2602 and the electrode system 2604 may be coupled, for example ata proximal end. In some embodiments, the electrode system 2604 is ableto move relative to the fixation system 2602. Deploying catheters in aserial fashion (target location, then fixation system, then electrodessystem) can allow the catheter diameters to be small and flexible (e.g.,compared to an all-in-one or combination systems).

To withdraw the system, the steps may be reversed with some access stepsomitted. For example, the sheath 2606 may be distally advanced tocapture the electrode system 2604, for example due to the tethers 2605helping to pull the electrode system 2604 into the sheath 2606. Thesheath 2606 including the electrode system 2604 may then be withdrawn.The fixation catheter 2620 may be advanced over the tether 2622 tocapture the fixation system 2602, and the fixation catheter 2620including the fixation system 2602 may be withdrawn. The dimensions inthis example method are not meant to be limiting to any particularembodiment (see, for example, other dimensions provided herein for thesetypes of elements).

In some embodiments, a single catheter could include the fixation system2602 and the electrode system 2604 (e.g., allowing integration of FIGS.26E-26H). In some embodiments, the fixation system 2602 may be proximalto the electrode system.

In some embodiments, the fixation system 2602 can be anchored in thedistal right pulmonary artery (e.g., delivering the fixation catheter2620 as far as it can extend before deploying the fixation system 2602),and the electrode system 2604 can be deployed in a more proximalposition. Fixation in the distal right pulmonary artery may be morestable and/or repeatable. The electrode system 2604 could berepositionable (e.g., able to slide, rotate) to map without modifyingthe position of the fixation system 2602. A proximal hub could comprisea locking mechanism to hold the electrode system 2604 in a set positionand/or an apposition device could secure the electrode system 2604.

FIG. 27A is a perspective view of another example of a fixation system2700. FIG. 27B is an elevational view of a portion of the fixationsystem 2700 of FIG. 27A. The fixation system 2700 comprises a fixationstructure 2702 and a fixation mechanism 2504. The fixation structure2702 may comprise, for example, a hypotube that has been cut and shapeset, a ribbon that has been shape set, and the like. The fixationstructure 2702 may be shape set, for example to flare radially outwardwhen not constrained by a catheter 2706. The fixation mechanism 2704 isillustrated as comprising a conical structure, but may comprise othershapes, for example, points or barbs. The fixation mechanism 2704 iscoupled to the fixation structure 2702 by a fixation arm 2703. In someembodiments, the fixation arm 2703 may be integral or monolithic withthe fixation structure 2702, for example being milled from the fixationstructure 2702. In some embodiments, the fixation arm 2703 is the samethickness as the fixation structure 2702. In some embodiments, thefixation arm 2703 a different thickness than the fixation structure2702, for example to provide different collapsing characteristics. Insome embodiments, the fixation arm 2703 may formed separately and thencoupled to the fixation structure 2702, for example by welding,soldering, etc. to the fixation structure 2702 in a hole or aperturethat has been milled in the fixation structure 2702. In someembodiments, the fixation arm 2703 may be integral or monolithic withthe fixation mechanism 2704, for example both being milled from a samepiece of material (e.g., the fixation structure 2702). In someembodiments, the fixation arm 2703 may formed separately and thencoupled to the fixation mechanism 2704, for example by welding,soldering, etc. The fixation arm 2703 is configured to flare radiallyoutward of the fixation structure 2702 when not constrained. Thefixation arm 2703 comprises a curved shape such that, when the fixationarm 2703 is constrained, for example by a catheter 2706, the fixationmechanism 2704 is radially inward of or below the outer surface of thefixation structure 2702.

FIGS. 27C-27F illustrate the fixation system 2700 of FIG. 27A beingretracted after engagement with tissue 2708. Prior to the stateillustrated in FIG. 27C, the system 2700 was advanced to a fixationsite. The system 2700 was advanced out of the catheter 2706, for exampleout of the side or out of the end of the catheter 2706. When notconstrained by the catheter 2706, the fixation structure 2702 may flareradially outwardly. When not constrained by the catheter 2706, thefixation arm 2703 may flare radially outwardly from the fixationstructure 2702 and engage the tissue 2708. For example, the fixation arm2703 may pivot or rotate at the point where the fixation arm 2703contacts the fixation structure 2702. In FIGS. 27D-27F, a catheter 2706advancing over the fixation arm 2703 causes the fixation arm 2703 toflex radially inwardly until, as shown in FIG. 27F, the fixationmechanism 2704 is radially inward of or below the outer surface of thefixation structure 2702. In FIG. 27D, the fixation structure 2704 ispulled out of the tissue 2708 in the same direction as the initialinteraction with the tissue 2708, which can be gentle on the tissue 2708(e.g., reducing or preventing endothelial damage such as snagging,tearing, scratching, etc.).

FIG. 27G is an elevational view of yet another example of a fixationsystem 2750. The fixation system 2750 is similar to the fixation system2700, comprising a fixation structure 2752, a fixation mechanism 2754,and a fixation arm 2753, but the fixation arm 2753 is not configured tomove relative to the fixation structure 2752. FIG. 27G also illustratesthe fixation arm 2753 having an end shape configured to correspond to ashape of the base of the fixation mechanism 2754 (e.g., annular for aconical fixation mechanism 2754). FIG. 27H is a side view of thefixation system 2750 of FIG. 27G. The fixation arm 2753 is spacedradially inward from the outer surface of the fixation structure 2752 bya first cavity 2755. The fixation arm 2753 is spaced radially outwardfrom the inner surface of the fixation structure 2752 by a second cavity2757. When the fixation system 2750 is pressed against tissue, some ofthe tissue may enter the cavity 2755 and interact with the fixationmechanism 2754. The second cavity 2757 may allow the fixation arm 2753to bend or flex radially inward. When the fixation system 2750 is priedaway from tissue, for example by retracting the fixation structure 2752into a catheter, the tissue may exit the cavity 2755 and stopinteracting with the tissue.

FIG. 27I is a side view of still another example of a fixation system2760. The fixation system 2760 is similar to the fixation system 2750,comprising a fixation structure 2762, a fixation mechanism 2764, and afixation arm 2763, but the fixation arm 2763 is not configured to flex.The fixation arm 2763 is spaced radially inward from the outer surfaceof the fixation structure 2762 by a first cavity 2755, but is not spacedradially outward from the inner surface of the fixation structure 2762by a second cavity. When the fixation system 2760 is pressed againsttissue, some of the tissue may enter the cavity 2765 and interact withthe fixation mechanism 2764. The lack of a second cavity may allow thefixation arm 2763 to remain solid, which may increase likelihood oftissue engagement. When the fixation system 2760 is pried away fromtissue, for example by retracting the fixation structure 2762 into acatheter, the tissue may exit the cavity 2765 and stop interacting withthe tissue.

FIG. 28A is a side view of an example of a fixation system 2800. Thefixation system 2800 comprises a fixation structure 2802, distalfixation mechanisms 2804 a, and proximal fixation mechanisms 2804 b. Thedistal fixation mechanisms 2804 a extend distally from the distal end ofthe fixation structure 2802 (e.g., distal ends of cells formed by strutsof the fixation structure 2802). The distal fixation mechanisms 2804 aflare radially outward in an expanded position. Upon retraction of thefixation structure 2802, for example into a catheter, the distalfixation mechanisms 2804 a flex radially inwardly from proximal todistal. The proximal fixation mechanisms 2804 b extend proximally froman intermediate portion of the fixation structure 2802 (e.g., proximalends of cells formed by struts of the fixation structure 2802). Theproximal fixation mechanisms 2804 b flare radially outward in anexpanded position. Upon retraction of the fixation structure 2802, forexample into a catheter, the proximal fixation mechanisms 2804 b flexradially inwardly as described in further detail herein. FIG. 28B is anexpanded view of the circle 28B in FIG. 28A, which better illustratesthe radially outward flexing of the proximal fixation mechanism 2804 b(e.g., versus the other contours of the fixation system 2800). Thefixation mechanisms 2804 are shape-set to protrude outside the wall ofthe fixation structure 2802.

FIG. 28C is a partial elevational view of the fixation system 2800 ofFIG. 28A. The proximal fixation mechanisms 2804 b are coupled to thefixation structure 2802 at attachment points 2812. The proximal fixationmechanisms 2804 b may be integral or monolithic with the fixationstructure 2802 (e.g., cut from the same hypotube, for example asdescribed with respect to FIG. 28F). The strands proximal to theattachment points 2812 are tethers 2808 comprising twists or bends 2810.When a hypotube is cut to form an attachment point 2812, a proximalfixation mechanism 2804 b, a tether 2808, cell struts, etc., theattachment point 2812 naturally becomes radially offset (e.g., because alarge mass naturally wants to remain straight) such that the proximalfixation mechanism 2804 b is slightly radially inward of the cell strutsand the tether 2808. A similar phenomenon occurs at the connectingstruts 2817 (FIG. 28A) between cells. The cut hypotube may be shape setincluding, without limitation, flaring the fixation structure 2802radially outward from proximal to distal, flaring the fixationmechanisms 2804 a, 2804 b radially outward from the fixation structure2802 (e.g., so the fixation mechanisms 2804 a, 2804 b stand proudcompared to the fixation structure 2802), and twisting the tethers 2808.

FIG. 28D shows an example of a radiopaque marker 2814 coupled to aproximal fixation mechanism 2804 b. The radiopaque marker 2814 maycomprise a band, an identifiable shape (e.g., a rectangle, circle,etc.). In some embodiments, the radiopaque member 2814 protrudes outwardfrom the proximal fixation mechanism 2804 b. In some embodiments, theradiopaque member 2814 is flush with the proximal fixation mechanism2804 b. Other portions of the fixation system 2800 may comprise aradiopaque marker (e.g., other proximal fixation mechanisms 2804 b,distal fixation mechanisms 2804 a, fixation structure 2802, tethers2810, etc.)

FIG. 28E shows an example of a hole or opening or aperture 2816 in aproximal fixation mechanism 2804 b. In some embodiments, the hole 2816may be used to attach other components (e.g., radiopaque markers,fixation elements such as conical members, barbs, fixation arms, etc.),such as by crimping, welding, etc. Attaching certain structures mayprovide better control of certain properties, for example shape-setting.In some embodiments, the hole 2816 may help to capture tissue, forexample the edges of the hole 2816 apposing tissue penetrating the hole2816.

FIG. 28F is a flattened view of an example of a hypotube cut pattern2820. The cut pattern 2820 includes tethers 2808, attachment points2812, proximal fixation mechanisms 2804 b including holes 2816, fixationstructure 2802, and distal fixation mechanisms 2804 a. The cut patternalso shows ramped or tapered areas 2822. The tapered areas 2822 canengage the distal end of a catheter during retraction, and may help withturning the proximal fixation mechanisms 2804 b. In some embodiments, itmay be possible to cut a sheet and roll the sheet into a tube (e.g.,initially shape setting into a cylinder and then shape setting, ordirectly shape setting). The cut hypotube may be shape set, for exampleinto the shape shown in FIG. 28A.

FIG. 28G is an expanded view of the dashed square 28G in FIG. 28F. Inaddition to the other manners of shape setting described herein, a strut2824 adjacent to the proximal fixation mechanism 2804 b may be bent atan angle. FIG. 28H is a side view of the strut 2824 of FIG. 28G. Theproximal end 2826 of the proximal fixation mechanism 2804 b and thedistal end 2828 of the proximal fixation mechanism 2804 b are shown indotted lines behind the strut 2824. FIG. 28I is a side view of theproximal fixation mechanism 2804 b being bent radially outward. FIG. 28Jis a side view of the proximal fixation mechanism 2804 b being bentradially outward and the strut 2824 being bent at a bend point 2830.Referring again to FIG. 28H, the length x of the proximal fixationmechanism 2804 b is shown. In some embodiments, the bend point 2830 isabout 50% of x±20% (e.g., measured from the proximal end 2826 or thedistal end 2828, about 20% of x, about 30% of x, about 40% of x, about50% of x, about 60% of x, about 70% of x, ranges between such values,etc.). The more proximal the bend point 2830, the more the proximalfixation mechanism 2804 b protrudes radially outward. The more distalthe bend point 2830, the less the proximal fixation mechanism 2804 bprotrudes radially outward. The angle of the portion of the strut 2824proximal to the bend point 2830 relative to the portion of the strut2824 distal to the bend point 2830 is between about 20° and about 50°(e.g., about 20°, about 30°, about 40°, about 50°, ranges between suchvalues, etc.). In some embodiments, the distance y between the distalend of the proximal fixation mechanism 2804 b and the portion of thestrut 2824 distal to the bend point (or, in FIG. 28I, the unbent strut2824) in an unconstrained state is between about 0.02 inches and about0.06 inches (e.g., about 0.02 inches, about 0.03 inches, about 0.04inches, about 0.05 inches, about 0.06 inches, ranges between suchvalues, etc.), although factors such as vessel diameter, the length x,etc. may influence the distance y.

FIG. 28K is a side view of the strut 2824 being bent at the bend point2830. In contrast to FIG. 28J, the proximal fixation mechanism 2804 b isnot bent, although other parameters (e.g., bend angle, location of thebend point 2830, the distance y, etc.) may remain the same.

FIGS. 28L-28O show the proximal fixation mechanisms 2804 b rotatinginwardly during retrieval into a catheter 2806. In FIG. 28L, thefixation system 2800 is fully deployed. The proximal fixation mechanisms2804 b stand proud. The distal fixation mechanisms 2804 a also standproud, providing bidirectional fixation. In FIG. 28M, the fixationsystem 2800 is starting to be withdrawn into the catheter 2806. Theproximal fixation mechanisms 2804 b still stand proud. In FIG. 28N, thefixation system 2800 is further withdrawn into the catheter 2806. Theproximal fixation mechanisms 2804 b still rotate inwardly as the distalend of the catheter 2806 interacts with the tapered portions 2822. InFIG. 28O, the fixation system 2800 is further withdrawn into thecatheter 2806. The proximal fixation mechanisms 2804 b except for thedistal ends are in the catheter 2806. No snagging, scratching, etc.occurred during retraction. Further retraction of the fixation system2800 would place the remainder of the fixation structure 2802 and thedistal fixation mechanisms 2804 a in the catheter 2806.

Having the proximal fixation mechanisms 2804 b pointed distally canallow for improved performance during retrieval of the fixation system2800 (e.g., lower probability of the proximal fixation mechanisms 2804 bor any other part of the fixation system 2800 getting snagged by thedistal end of the catheter 2806). Since the proximal fixation mechanisms2804 b articulate radially inwards upon retrieval, the proximal fixationmechanisms 2804 b can be included with little concern of scratchingand/or engaging the inner surface of the catheter 2806 during deploymentor retrieval. The degree of inward flex of the proximal fixationmechanisms 2804 b during retrieval can be controlled by, for example,the location of the bend point 2830, the attachment point 2812, and/orbending of the proximal fixation mechanisms 2804 b. The distal end cancomprise distal fixation mechanisms 2804 a, which can provide resistanceto distal motion.

In some embodiments, the fixation mechanisms described herein may takethe form of a textured surface. For example, material may be added toand/or removed from a fixation arm or a fixation structure to form astippled, striped, rough, etc. surface. The texture may increase thesurface area, which can increase the amount of tissue that is engaged.

FIG. 29A illustrates an example of a catheter system 2900. The cathetersystem 2900 comprises a sheath 2906, a first loop 2902 extending from adistal end of the sheath 2906, and a second loop 2904 extending from thedistal end of the sheath 2906. At least one of the first loop 2902 andthe second loop 2904 comprises a plurality of electrodes 2908. In someembodiments, the catheter system 2900 comprises fixation features 2910(e.g., comprising atraumatic stiff loops).

FIGS. 29B-29F illustrate an example method of deploying the cathetersystem 2900 of FIG. 29A. In FIG. 29B, the sheath 2906 has been advancedpast the pulmonary valve 2928 into the pulmonary trunk 2922. Thepulmonary valve 2928 is a tricuspid valve. In some embodiments, thesheath 2906 may have a shape configured to interact with the cuspids ofthe pulmonary valve 2928. The sheath 2902 may comprise a pressure sensorproximate to a distal end to help a user determine when the distal endof the sheath 2906 is distal to the pulmonary valve 2928. FIG. 29A alsoillustrates the right pulmonary artery 2924, the left pulmonary artery2926, the bifurcation 2925 between the right pulmonary artery 2924 andthe left pulmonary artery 2926, and a target nerve 2920 (e.g., the rightstellate CPN).

In FIG. 29C, the loops 2902, 2904 are deployed from the distal end ofthe sheath 2906. In some embodiments, the loops 2902, 2904 are deployedsubstantially simultaneously, which can reduce delivery complexity, forexample using a single actuation mechanism having a short deliverythrow. In some embodiments, the loops 2902, 2904 may be deployedsequentially or serially or staggered with either loop being deployedfirst, which can reduce the profile of the catheter system 2900. Theloops 2902, 2904 may be in any rotational orientation.

In FIG. 29D, the sheath 2906, with the loops 2902, 2904 deployed, isadvanced towards the bifurcation 2925. The loops 2902, 2904 self-orientinto the right pulmonary artery 2904 and left pulmonary artery 2906,regardless of the original rotational orientation of the loops 2902,2904. For example, the catheter system 2900 may rotate during distaladvancement in response to the loops 2902, 2904 interacting with theanatomy.

In FIG. 29E, the sheath 2906 is further distally advanced towards thebifurcation 2925. The loops 2902, 2904 may advance further into theright pulmonary artery 2924 and the left pulmonary artery 2926,respectively, but advancement is limited by the bifurcation 2925. InFIG. 29F, fixation features 2910 may optionally be deployed from thesheath 2906, for example proximate to the pulmonary valve 2928. Thefixation features 2910 may bias the sheath 2906 distally towards thebifurcation 2925, which can limit distal advancement. In someembodiments, the fixation features 2910 comprise a shape memory materialsuch as nitinol. Blood flow is in the distal direction, which can helpto maintain the positions of the loops 2906. In some embodiments, thesheath 2906 may comprise features to interact with the blood flow (e.g.,fins, a balloon, etc.).

The electrodes 2908 of the first loop 2902 and the electrodes 2908 ofthe second loop 2904 may be activated according to a predetermined orlogical sequence to determine which loop 2902, 2904 can modulate thetarget nerve 2910. The electrodes 2908 of the selected loop may be usedfor neuromodulation and the electrodes 2908 of the other loop may bedeactivated.

In some embodiments, only the first loop 2902 comprises electrodes 2908.The second loop 2904 may still provide self-orientation and interactionwith the bifurcation 2925. The electrodes 2908 of the first loop 2902may be activated according to a predetermined or logical sequence todetermine if the first loop 2902 can modulate the target nerve 2910. Ifthe first loop 2902 is determined to not be able to modulate the targetnerve 2910, the catheter system 2900 may be repositioned (e.g.,including rotating, for example) 180° so that the first loop 2902 is inthe other of the right pulmonary artery 2924 and the left pulmonaryartery 2926.

In some embodiments, rather than loops 2902, 2904, a catheter systemcomprises two fingers having pigtail ends. The pigtail ends may providethe same benefits, for example bifurcation interaction, as the loops2902, 2904, and reduce potential issues such as poking the vasculature,bending, etc.

In some embodiments, neither of the loops 2902, 2904 compriseselectrodes 2938. In certain such embodiments, the electrodes 2938 may bedisposed on the sheath 2906. FIG. 29G illustrates an example of acatheter system 2930. The catheter system 2930 comprises a sheath 2906,a first loop 2902 extending from a distal end of the sheath 2906, and asecond loop 2904 extending from the distal end of the sheath 2906. Thesheath 2906 comprises a plurality of electrodes 2938. In someembodiments, the catheter system 2930 comprises fixation features 2910(e.g., comprising atraumatic stiff loops). The loops 2902, 2904 mayinhibit or prevent distal migration and/or the fixation features 2910may inhibit or prevent proximal migration. The catheter system 2930 maybe positioned as described with respect to the catheter system 2900, forexample passing distal to the pulmonary valve, deploying the loops 2902,2904, and advancing towards a bifurcation where one loop 2902 extendsinto one branch vessel and the other loop 2904 extends into the otherbranch vessel.

The electrodes 2938 may be annular, partially annular, points, etc. Insome embodiments, for example in which the electrodes 2938 are on oneside of the sheath 2906, the electrodes 2938 may be activated accordingto a predetermined or logical sequence to determine if the target nerveis captured. If the target nerve is not captured, the catheter system2930 may be repositioned (e.g., including rotating, for example 180°) sothat the first loop 2902 is in the other of the right pulmonary artery2924 and the left pulmonary artery 2926. In some embodiments in whichone or both of the loops 2902, 2904 comprise electrodes 2908, the sheath2908 may comprise electrodes 2938.

In some embodiments, electrodes that are separate from the loops 2902,2904 may be deployed from the catheter 2906. For example, cathetersystems described herein provide electrode matrices that can be deployedfrom a side of a catheter and/or an end of a catheter. In certain suchembodiments, the loops 2902, 2904 can be used to orient and position thecatheter 2906 at a target site, and then an electrode matrix can bedeployed from the catheter 2906 at the target site.

In some embodiments, rather than being a plain loop, at least one of theloops 2902, 2904 may be modified, for example as described herein withrespect to other catheter systems. In some embodiments, each of theloops 2902, 2904 may be modified differently.

FIG. 29H illustrates an example of a catheter system 2940. The cathetersystem 2940 comprises a sheath 2906, a first loop 2942 extending from adistal end of the sheath 2906, and a second loop 2904 extending from thedistal end of the sheath 2906. The first loop 2942 comprises a firstwire 2943 a and a second wire 2943 b. Each of the wires 2943 a, 2943 bcomprises electrodes 2948, forming an electrode matrix. Distal to thedistal end of the sheath 2906, the first wire 2943 a and the second wire2943 b are spaced to form a gap 2943 c that spaces the electrodes 2948on the wire 2943 a from the electrodes 2948 on the wire 2943 b. Morewires and electrodes are also possible. For example, a third wire mayextend between the first wire 2943 a and the second wire 2943 b. Theelectrodes 2948 are shown as button electrodes, but other types ofelectrodes are also possible (e.g., barrel, within a U-channel, etc.).

In some embodiments, the catheter system 2940 comprises fixationfeatures 2910 (e.g., comprising atraumatic stiff loops). The cathetersystem 2940 may be positioned as described with respect to the cathetersystem 2900, for example passing distal to the pulmonary valve,deploying the loops 2942, 2904, and advancing towards a bifurcationwhere one loop 2942 extends into one branch vessel and the other loop2904 extends into the other branch vessel.

FIG. 29I illustrates an example of a catheter system 2950. The cathetersystem 2950 comprises a sheath 2906, a first loop 2952 extending from adistal end of the sheath 2906, and a second loop 2904 extending from thedistal end of the sheath 2906. The first loop 2952 comprises a wirehaving an undulating or zig-zag or sinusoidal or wave shape. The firstloop 2952 comprises electrodes 2958 at peaks and valleys, forming anelectrode matrix. The electrodes 2958 may also or alternatively bepositioned between peaks and valleys. The first loop 2952 may compriseadditional wires and/or electrodes. For example, a second wire, whichmay be straight, sinusoidal, or another shape, may extend along thefirst wire. The electrodes 2958 are shown as button electrodes, butother types of electrodes are also possible (e.g., barrel, within aU-channel, etc.). In some embodiments, a sinusoidal shape may be in aplane configured to transversely appose a vessel wall. In certain suchembodiments, electrodes are at sinusoidal peaks, which can provideincreased or optimum vessel wall contact. In some embodiments, asinusoidal shape can increase rigidity, which can improve wallapposition, for example compared to a straight shape.

In some embodiments, the catheter system 2950 comprises fixationfeatures 2910 (e.g., comprising atraumatic stiff loops). The cathetersystem 2950 may be positioned as described with respect to the cathetersystem 2900, for example passing distal to the pulmonary valve,deploying the loops 2952, 2904, and advancing towards a bifurcationwhere one loop 2952 extends into one branch vessel and the other loop2904 extends into the other branch vessel.

Several processes described herein are provided with respect to enteringthe pulmonary trunk and then advancing into the right pulmonary arteryand/or the left pulmonary artery, or more generically entering a main orafferent vessel and advancing into one or more efferent or branchvessels. In some embodiments, a catheter system may enter from a branchvessel and be advanced towards a main vessel and/or another branchvessel. For example, a catheter system may be inserted into the rightinternal jugular vein and advanced towards a superior vena cava. Foranother example, a catheter system may be inserted into the leftinternal jugular vein and advanced towards a left brachiocephalic vein.

FIG. 29J illustrates another example of a catheter system 2960. Thecatheter system 2960 comprises a sheath 2906 and a loop 2962. The loop2962 is configured to extend from a distal end of the sheath 2906 and tobend proximally back towards the sheath 2906. In some embodiments, forexample as described with respect to the catheter system 2900, the loop2962 may comprise electrodes. In some embodiments, the catheter system2960 comprises fixation features 2910 (e.g., comprising atraumatic stiffloops). For example as described with respect to the catheter system2930, the sheath 2906 comprises electrodes 2968. In some embodiments,the catheter system 2960 comprises sheath electrodes 2968 and theelectrodes on the loop 2962.

FIG. 29K illustrates another example of a catheter system 2965. Thecatheter system 2965 is similar to the catheter system 2960 except thatthe loop 2963 is configured to extend from a side of the sheath 2906,through an aperture 2907, and to bend proximally. In some embodiments,the aperture 2907 may comprise turning features such as a ramp.

FIGS. 29L-29N illustrate an example method of deploying the cathetersystem 2965 of FIG. 29K. The example method may also or alternatively beused to deploy the catheter system 2960 of FIG. 29J or other cathetersystems. The vasculature illustrated in FIGS. 29L-29N includes the leftinnominate vein or left brachiocephalic vein 2955, the left subclavianvein 2961, and the left internal jugular vein 2964, described in furtherdetail herein with respect to FIG. 2I, although other the method mayalso be appropriate for use at other vascular or other lumenbifurcations. The catheter systems can be adjusted to better interactwith a Y-shaped bifurcation, a T-shaped bifurcation, from an afferentvessel, from an efferent vessel, depending on the relative sizes of thevessels, etc. In some embodiments, such catheter systems canadvantageously positively locate the catheter at anatomical junctions.Certain such anatomical junctions may have known passing nerves, whichcan allow the user to locate electrodes in a precise location withreduced or minimal or no visualization (e.g., fluoroscopy) and/orguidance (e.g., use of a guidewire and/or guide catheter). In someembodiments, the Y-shaped or T-shaped anatomy may help ensure that thecatheter and electrodes remain fixed in place.

In FIG. 29L, the catheter system 2965 is in the left internal jugularvein 2964, which may the point at which the vasculature is accessed byan introducer. The catheter system 2965 is advanced towards the leftbrachiocephalic vein 2955. At least during advancing past the junctionof the left subclavian vein 2961 and the left internal jugular vein2964, the loop 2963 is deployed out of the sheath 2906. As the sheath2906 is advanced in the left internal jugular vein 2964, the loop 2963is inwardly compressed slides along the wall of the left internaljugular vein 2964.

In FIG. 29M, the catheter system 2965 is advanced far enough that theloop 2963 is unconstrained and able to outwardly expand to a set shape.In FIG. 29N, the catheter system 2965 is retracted until the loop 2963contacts the left subclavian vein 2961. The catheter system 2965 can berepeatably placed at the junction between the left subclavian vein 2961and the left internal jugular vein 2964. In some embodiments, placementcan be without fluoroscopy, for example using distance and/or tactilechanges to determine that the catheter system 2965 is properlypositioned. Fixation features 2910 may optionally be deployed from thesheath 2906, for example proximate to the junction in the left internaljugular vein 2964. The electrodes 2968 can be positioned along thesheath 2906 to capture a target nerve 2921. The target nerve 2921 maycomprise, for example, a thoracic cardiac branch nerve. In someembodiments, the target nerve 2921 is a cervical cardiac nerve. Cervicalcardiac nerves may also or alternatively be targeted from the leftinternal jugular vein 2964. In some embodiments, the catheter system2965 comprises features that may help to capture a target nerve. Forexample, the sheath 2906 may comprise a curvature to bend towards theposition 2921, the catheter system 2965 may comprise a second loopcomprising electrodes and configured to be deployed out of the distalend or the side of the sheath 2906 in a direction opposite the loop2963, and/or the electrodes 2968 may be longitudinally aligned withand/or distal to the aperture 2907.

FIG. 30A is a perspective view an example of an electrode system 3000.The system 3000 comprises a catheter 3006, a framework 3002, and aplurality of electrodes 3008. FIG. 30B is a top plan view of a portionof the electrode system 3000 of FIG. 30A. The catheter 3006 comprises aproximal segment 3010 having a generally circular cross-section and adistal segment 3012 having a generally oval cross-section. The roundshape of the proximal segment 3010 can be useful, for example, to coupleto round proximal components such as luer fittings, other roundcatheters, etc. The oval shape of the distal segment 3012 can be useful,for example, to preferentially align near the target zone, which canreduce or minimize distance from the sheath 3006 to the target zone. Theoval shape of the distal segment 3012 can be useful, for example, toresist torque and rotation. The framework 3002 may comprise, forexample, two shape memory (e.g., nitinol) wires forming a zig-zag orundulating or sinusoidal pattern or serpentine to create a wave frame oraccordion shape. The framework 3002 can be substantially level orplanar, or can comprise a curve, for example to bias or conform to avessel wall. Leads or conductor wires coupling the electrodes 3008 to amodulation system can run along and/or through the framework 3002.

The electrodes 3008 comprise buttons coupled to the framework 3002. Insome embodiments, the electrodes 3008 have a diameter between about 1 mmand about 3 mm (e.g., about 1 mm, about 1.5 mm, about 2 mm, about 2.5mm, about 3 mm, ranges between such values, etc.). The electrodes 3008are longitudinally offset, as shown by the dashed lines in FIG. 30B, tosequentially nest in catheter 3006 the before deployment and/or uponretraction, which can reduce the profile of the catheter. In someembodiments, at least some of the electrodes 3008 may be side-by-side.In some embodiments, one side of the electrodes 3008 is insulated, whichcan provide directional electrodes 3008. The electrodes 3008 may becoupled to the framework 3002 to inhibit rotation of the electrodes3008, for example keeping the surfaces of the electrodes 3008 generallylevel or planar. Interaction with tissue such as a vessel wall mayinduce the framework 3002 to bend before inducing the electrodes 3008 torotate.

FIG. 30C is a perspective view of another example of an electrode system3020. Similar to the system 3000, the system 3020 comprises a catheter3006, a framework 3002, and a plurality of electrodes 3028. FIG. 30D isa distal end view of the electrode system 3020 of FIG. 30C in acollapsed state. FIG. 30E is a distal end view of the electrode system3020 of FIG. 30C in an expanded state. The expanded state shown in FIGS.30C and 30E is partially expanded, as some electrodes 3028 remain in thecatheter 3006. A selected number of electrodes 3028 may be deployed asdetermined by the user (e.g., based on the subject's anatomy, theindication, etc.).

The electrodes 3028 comprise barrel-shapes coupled to the framework3002. The framework 3002 may include longitudinal segments rather thanpeaks to accommodate the lengths of the electrodes 3008, and the bendsin the framework 3002 can maintain longitudinal positioning of theelectrodes 3028. In some embodiments, the electrodes 3028 have adiameter between about 0.01 in and about 0.1 in (e.g., about 0.01 in,about 0.02 in, about 0.03 in, about 0.04 in, about 0.05 in, about 0.06in, about 0.08 in, about 0.1 in, ranges between such values, etc.). Insome embodiments, the electrodes 3028 have a length between about 0.02in and about 0.2 in (e.g., about 0.02 in, about 0.03 in, about 0.04 in,about 0.05 in, about 0.06 in, about 0.07 in, about 0.08 in, about 0.09in, about 0.1 in, about 0.12 in, about 0.15 in, 0.2 in, ranges betweensuch values, etc.). The edge electrodes 3028 are laterally side-by-side,which can provide certain electrode combination patterns (e.g., asdiscussed with respect to FIGS. 32A-32D). In some embodiments, a centralelectrode 3028 can be a cathode and the four closest lateral electrodes3028 can be anodes. In some embodiments, the electrodes 3028 may belaterally offset (e.g., like the electrodes 3008). In some embodiments,a circumferential arc of the electrodes 3028 is insulated, which canprovide directional electrodes 3028. The electrodes 3028 may be coupledto the framework 3002 to inhibit rotation of the electrodes 3028, forexample maintaining uninsulated surfaces of the electrodes 3028 facing acertain direction. Other shapes of the electrodes 3028 are also possible(e.g., cylindrical, spherical).

The system 3020 comprises an optional core element 3024. The coreelement may, for example, help to carry conductor wires and/or tomaintain a shape of the framework 3002. In some embodiments, the coreelement 3024 comprises a round tube (e.g., a hypotube). In someembodiments, the core element 3024 is flat or ribbon shaped,rectangular, oval, or other shapes. In some embodiments, the coreelement 3024 is laterally offset from a center of the framework 3002.

FIG. 30F is a plan view of yet another example of an electrode system3030. Similar to the system 3000, the system 3030 comprises a framework3002 and a plurality of electrodes 3038. The system 3030 comprises asheet or membrane or mesh 3032. In contrast to the systems 3000, 3020,the electrodes 3038 of the system 3030 are on the sheet 3032 comprisinga flexible material (e.g., polyimide, silicone). The sheet 3032 maycomprise, for example, a flex circuit including patterned conductorwires. The sheet 3032 may comprise, for example, a mesh such asdescribed with respect to FIG. 4C. The sheet 3032 holding the electrodes3038 can provide control of the relative positions and spacing of theelectrodes 3038.

The system 3030 optionally comprises a core element 3034. The framework3032 may be coupled to the core element 3034, for example as individualV-shaped segments. The sheet 3032 is coupled to the framework 3002, andoptionally to the core element 3034. In some embodiments, the framework3002 and the sheet 3034 wrap around the core element 3034 in a collapsedstate. The system 3030 can be delivered in a collapsed state without acatheter (e.g., tracking the core element 3034 over a guidewire ortether), for example if the sheet 3032 at least partially thermallyinsulates the framework 3002 such that thermal shape memory is slow totake effect. FIG. 30G is a distal end view of the electrode system 3030of FIG. 30F. In the deployed state, as best seen in FIG. 30G, the sheet3032 has a curved shape, which can help to hold the electrodes 3038against a vessel wall.

FIGS. 31A and 31B show example electrode combinations for nineelectrodes in a 3×3 matrix. Other numbers of electrodes and patterns ofmatrices can be used, and the 3×3 matrix is shown only for the sake ofdiscussion. In embodiments in which a power supply is external to thesubject, energy budget may be of less concern than accurate tissue nervetargeting. A sequence of combinations in which a first electrode iscathodic and a second electrode is anodic can be tested to see whichcombinations provide certain effects (e.g., effecting contractilityand/or not affecting heart rate). A subject could provide inputregarding pain, cough, general discomfort, tingling, and/or othersensations during the process to give the system feedback about whichelectrode combinations cause those effects. The contractility responsecould be measured, for example via a pressure sensor, accelerometer, orother contractility measurement, including external tools such as echoultrasound.

FIG. 31A shows an example sequence of twelve combinations in which oneelectrode is anodic and one electrode is cathodic. Each combination maybe operated, for example, 4 ms, followed substantially immediately bythe next combination in the sequence. The sequence may be repeated ifthe initial run was successful, for example about 50 ms (20 Hz) later.After running the sequence of tests 1-12, combinations of electrodesthat have an effect above or below a certain threshold may be identifiedfor use and/or non-use in calibration stimulation and/or therapeuticstimulation. This can automate the mapping of the nerve location andincrease or optimize stimulus response for efficacy and tolerance. FIG.32A shows that other combinations of these same electrodes are alsopossible, for example, with an electrode in the middle, diagonal, etc.The same sequence or a shorter sequence (e.g., comprising tests 1, 2, 7,and 8) may be used to verify positioning on a macro level (e.g., thatsome combination of electrodes in that matrix position providesstimulation), for example upon initial positioning, repositioning,and/or periodically to check for matrix migration.

In some embodiments, a monopolar mode in which one electrode in thematrix is made cathodic with an anodic body patch (or vice versa) on thesubject's chest, back, or arm can be used before bipolar combinations ofelectrodes to find nerve faster, and then bipolar or guarded bipolar orbullseye (e.g., as discussed herein) combinations can be used to moreselectively capture the nerve.

In some embodiments, a plurality of sequences may be available (e.g.,having at least one electrical parameter or electrode combinationsequence that is different). For example if a first sequence causes morethan a threshold number of undesired responses, a second sequence maystart, and so on. The system may return to an initial sequence based onresults of other sequences.

Sequences of combinations in which a plurality of electrodes arecathodic and one electrode is cathodic, in which one electrode is anodicand a plurality of electrodes are cathodic, and in which a plurality ofelectrodes are anodic and a plurality of electrodes are cathodic arealso possible.

FIGS. 32A-32D show example electrode combinations for twelve electrodesin a 3×4 matrix. The 3×4 matrix is an example, and other matrices arealso possible (for example, but not limited to, 2×2, 2×3, 2×4, 2×5, 3×3,3×5, 4×4, 5×5, reversals (e.g., 3×2 being a reversal of 2×3), etc.). Insome embodiments, the matrix may be irregularly shaped, for example,being 2×2 and then 3×3. In FIGS. 32C and 32D, the middle column isoffset relative to the left and right columns. The electrodecombinations of FIGS. 32A-32D may be called “guarded bipolar”combinations because the cathode is completely surrounded by anodes, oris at least not adjacent to a non-anodic cathode. In FIG. 32A, thecathodic electrode in row 2, column 2 is surrounded by anodic electrodesin row 1, row 3, and row 2, columns 1 and 3. In FIG. 32B, the cathodicelectrode in row 4, column 2 is surrounded by anodic electrodes in row3, and row 4, columns 1 and 3. In FIG. 32C, the cathodic electrodecolumn 2, second from the top is surrounded by anodic electrodes incolumn 1, first two from the top, column 3, first two from the top, andcolumn 2, first and third from the top. In FIG. 32D, the cathodicelectrode column 2, first from the bottom is surrounded by anodicelectrodes in column 3, first from the bottom, column 2, first from thebottom, and column 3, second from the bottom. Guarded cathodes (usingtwo or more anodes) can allow for controlling the spread of the electricfield, which can provide a more efficient stimulation to the targetnerve, and/or which can reduce spillover of the electric field tonon-target nerves, which could cause unintended side-effects.

In some embodiments, an electrode matrix can be used to electronicallyreposition the electrodes. For example, referring to FIG. 32A, if all ofthe anodes and cathodes are shifted down one row such that the cathodicelectrode in row 3, column 2 is surrounded by anodic electrodes in row2, row 4, and row 3, columns 1 and 3. Referring again to FIG. 31A,changing from test 3 to test 9, from test 1 to test 11, etc. could beconsidered electronic repositioning. Electrodes may thereby beelectronically repositioned in multiple directions. In electronicrepositioning, the electrode matrix itself does not move or migrate.Electronic repositioning may be used to counter unintended movement ormigration of the electrode matrix.

In some embodiments, the stimulation comprises an active biphasicwaveform in which area under a curve is actively managed to be zero byforcing a pulse in opposite charge over a longer duration by measuringcharge. In some embodiments, the stimulation comprises a passivebiphasic waveform in which area under a curve is zero by allowing thecharge to dissipate from the tissue.

In some embodiments, the stimulation comprises an amplitude betweenabout 1 mA and about 20 mA (e.g., about 1 mA, about 2 mA, about 3 mA,about 4 mA, about 5 mA, about 6 mA, about 7 mA, about 8 mA, about 9 mA,about 10 mA, about 15 mA, about 20 mA, ranges between such values,etc.). Lower amplitudes may advantageously have less penetration depth,which can inhibit or avoid stimulation of nerves or other tissue that isnot targeted. Higher amplitudes may advantageously be more likely tohave a therapeutic effect. In some embodiments, the stimulationcomprises a pulse width between about 0.5 ms and about 4 ms (e.g., about0.5 ms, about 0.75 ms, about 1 ms, about 1.25 ms, about 1.5 ms, about1.75 ms, about 2 ms, about 2.25 ms, about 3 ms, about 4 ms, rangesbetween such values, etc.). In some embodiments, lower amplitude (e.g.,less than about 10 mA) can be used in combination with a pulse widthaccording to a strength-duration curve to provide the desired effect.Lower amplitudes may advantageously have less penetration depth, whichcan inhibit or avoid stimulation of nerves or other tissue that is nottargeted. Higher amplitudes may advantageously be more likely to have atherapeutic effect. In some embodiments, a lower amplitude (e.g., lessthan about 10 mA) can be used in combination with a pulse widthaccording to a strength-duration curve to provide the desired effect.

In some embodiments, the stimulation comprises a frequency between about2 Hz and about 40 Hz (e.g., about 2 Hz, about 5 Hz, about 10 Hz, about15 Hz, about 20 Hz, about 25 Hz, about 30 Hz, about 40 Hz, rangesbetween such values, etc.). Lower frequencies (e.g., less than about 10Hz) may advantageously have negligible effect on pain receptors thatgenerally respond to much higher frequencies such that a subject is moretolerant of the therapy.

In some embodiments, the stimulation is ramped at a beginning and/or anend of the stimulation duration. For example, if stimulation duration is10 seconds, the initial stimulation burst may be about 50% based on atleast one parameter (e.g., ON duration, amplitude, pulse width,frequency, etc.), then increased or ramped up to 60%, 70%, etc. over thecourse of 2 seconds until reaching 100%. After 6 seconds at 100%, thestimulation may be decreased or ramped down to 95%, 90%, etc. over thecourse of 2 seconds until reaching 50%, after which the stimulation maybe turned off. Ramping up and/or down may reduce side effects, increasesubject tolerance, and/or avoid shocks to the system that may occur withan initial full burst. The duration of the ramp(s) may be based on apercentage of stimulation duration (e.g., 20% ramp up, 20% ramp down),absolute durations (e.g., 2 seconds ramp regardless of stimulationduration), or other factors. The ramp may be linear or take some otherfunction (e.g., decreasing steps for a ramp up, increasing steps for aramp down). In embodiments in which a ramp up and a ramp down are used,the ramp up may be different than the ramp down (e.g., startingpercentage may be different than end percentage, ramp up duration may bedifferent than ramp down duration, ramp up function may be differentthan ramp down duration, etc.).

FIG. 33A is a plot of contractility versus stimulation. Starting from abaseline contractility, the stimulation is turned ON for Time 1. Thereis some time delay for the stimulation to result in a change incontractility (e.g., about 10 to 20 seconds), after which contractilitysteadily climbs until reaching a fairly steady state. When contractilityis turned OFF in time 2, there is some time delay before thecontractility begins to decay. The decay delay when stimulation is OFFis longer than the delay when stimulation is ON. The time to ramp up toa baseline level during the decay is also less than from a baseline. Thedecay may also be reduced over time. Accordingly, the stimulation ON andOFF do not perfectly correlate to the durations when contractilitychanges.

In some embodiments, stimulation is turned ON for 5 seconds, followed bystimulation being turned OFF for 10 seconds. In some embodiments,stimulation is turned ON for 2 seconds, followed by stimulation beingturned OFF for 5 seconds. In some embodiments, stimulation is turned ONfor 10 seconds, followed by stimulation being turned OFF for 30 seconds.In some embodiments, stimulation is turned ON until a substantiallysteady state is achieved, followed by stimulation being turned OFF untila certain contractility is reached, at which point the stimulation isturned ON until the substantially steady state is again achieved, etc.Such an approach can reduce or minimize an effective dose. A duty cycleapproach in view of this discovery can reduce the amount of time thatstimulation is ON, which can reduce energy usage, maintain therapeuticeffect, and/or reduce side effects, which can increase patient comfortand tolerability.

In some embodiments, a ramping feature could be used to slowly ramp theintensity of the stimulation ON and OFF, or to shut the stimulation OFFquickly. A ramping feature can allow the patient to adapt to stimulationand reduce sudden transitions. For example, at least one parameter(e.g., ON duration, amplitude, pulse width, frequency, etc.) could beslowly increased and/or decreased over time until building towards afinal value.

In some embodiments, for example for short term treatment, a duty cyclemay comprise alternating ON for 5 seconds and OFF for 5 seconds for 1hour. In some embodiments, for example for short term treatment, a dutycycle may comprise alternating ON for 5 seconds and OFF for 10 secondsfor 1 hour. In some embodiments, for example for short term treatment, aduty cycle may comprise alternating ON for 10 minutes and OFF for 50minutes for 1 hour. In some embodiments, for example for long termtreatment, a duty cycle may comprise alternating ON for 1 hour and OFFfor 1 hour for 1 day. In some embodiments, for example for long termtreatment, a duty cycle may comprise alternating ON for 1 hour and OFFfor 1 hour for 1 day. In some embodiments, for example for long termtreatment, a duty cycle may comprise alternating ON for 1 hour and OFFfor 23 hours for 1 day. The ON durations in long term treatment mayinclude the cycling of the short term treatments. For example, ifalternating ON for 1 hour and OFF for 1 hour for 1 day, the durations inwhich stimulation is ON for 1 hour may comprise alternating ON for 5seconds and OFF for 5 seconds for that 1 hour. In some embodiments, aplurality of different ON/OFF cycles may be used during a long term ONduration, for example 10 seconds ON and 10 seconds OFF for 1 minute,then 1 minute ON and 5 minutes OFF for 10 minutes, then 10 minutes ONand 50 minutes OFF for 4 hours, for a long term ON duration of 4 hoursand 11 minutes. Short term and/or long term ON/OFF cycles may be atleast partially based on a patient state (e.g., awake or sleeping,laying down or upright, time since initial stimulation, etc.).

FIG. 33B is a plot of contractility versus stimulation using athreshold-based approach and an optimized duty cycle. Stimulation isturned ON and OFF for some duration. As noted above, the decay ofcontractility after the duration is reduced such that contractilityremains above a threshold for a certain duration. This duration may beknown or determined, for example by sensing contractility. The brokenline in FIG. 33B shows a time when the determination is made to restartthe stimulation cycle for another duration. This process may be repeatedfor the time that the subject is being treated, until a recalibration,etc.

FIG. 34 is an example process flow that can be used to implement a dutycycle method, for example as described with respect to FIGS. 33A and33B. Stimulation is turned ON for 5 seconds, then OFF for 5 seconds,then repeated for 10 minutes, after which stimulation is turned OFF forone hour. The process flow of FIG. 34 then begins. Starting with cardiacstimulation OFF, a physiologic signal is monitored. A baseline trend isstored. The current signal is checked for deviation from the trend by aphysician-set threshold (e.g., less than or greater than a certainquantity, percentage, etc.). If the current signal has not deviated, thecardiac stimulation remains OFF and the physiologic signal continues tobe monitored and the baseline trend stored until the current deviates.When the current deviates from the trend, cardiac stimulation is turnedON. A patient monitor report is sent to the physician. At periodicintervals, the physiologic signal is rechecked to see if the trend isback to baseline. If the trend is not back to baseline, the cardiacstimulation remains ON. If the trend is back to baseline, the cardiacstimulation is turned OFF and the process starts all over.

In some embodiments, the system comprises one or more of the following:means for modulation (e.g., an electrode or other type of stimulationcatheter or delivery device), means for fixation (e.g., barbs, prongs,anchors, conical structures, or other types of fixation mechanisms),means for sensation (e.g., a sensor integral with a catheter, on aseparate catheter, external to a subject), and means for calibration(e.g., predetermined or logical sequences of determining stimulationparameters).

Several embodiments of the invention are particularly advantageousbecause they include one, several, or all of the following benefits: (i)increasing contractility (e.g., left ventricle), (ii) not affectingheart rate or affecting heart rate less than contractility, (iii)providing an anchoring or fixation system to resist movement, (iv),and/or (x)

FIG. 35A schematically illustrates a mechanically repositionableelectrode catheter system 3500. The system 3500 comprises a proximalportion a handle or hub 3502. The handle 3502 includes a mechanicalrepositioning system 3504 including a track or channel or groove 3510and a knob 3512 slideable within the groove 3510. The system 3500further comprises a sheath 3506 and an electrode system 3508. Theelectrode system 3508 may be movable in and out of the sheath 3506. FIG.35A shows the electrode system 3508 already expanded out of the sheath3506. The knob 3512 is coupled to the electrode system 3508 such thatlongitudinal and/or rotational movement of the knob 3512 results incorresponding longitudinal and/or rotational movement of the electrodesystem 3508. The sheath 3506 may be separately anchored in thevasculature, for example as described herein, such that only theelectrode system 3508 moves upon movement of the knob 3512.

In some embodiments, longitudinal movement of the knob 3512 results inthe same or 1:1 longitudinal movement of the electrode system 3508. Insome embodiments, gears or other mechanical devices can be used to makethe movement ratio more than 1:1 or less than 1:1. Pulleys and othermechanical devices can be used to reverse movement of the knob 3512.FIG. 35A shows a detent groove 3522 in the sheath 3506, which caninteract with a detent coupled to the electrode system 3508 and/or theknob 3512, for example as described with respect to FIG. 35B. In FIG.35A, the knob 3512 has already been longitudinally advanced enough, froma proximal position, that the electrode system 3508 is deployed out ofthe sheath 3506.

In some embodiments, the electrodes of the electrode system 3508 may bestimulated to test the effect of certain pairs of electrodes. If none ofthe electrodes pairs has an effect, the electrode system 3508 may bemoved using the repositioning system 3504 and the test rerun. In someembodiments, a distal-most electrode pair may have the most effect, butnot as large an effect as may have been expected. The electrode system3508 may be advanced distally to better test the effects of theelectrodes distal to the original site.

FIG. 35B illustrates the catheter system 3500 of FIG. 35A afterlongitudinal advancement. Compared to FIG. 35A, the knob 3512 haslongitudinally advanced a distance 3514. Movement of the knob 3512 canbe manual, electronic, mechanical, combinations thereof, and the like.The electrode system 3508 has also longitudinally advanced a distance3514. The electrode system 3508 is coupled to a detent 3520. Forexample, the detent 3520 may be coupled to a hypotube, a wire, etc. Whenthe detent 3520 reaches a certain longitudinal position, the detent 3520may extend into the detent groove 3522 in the sheath 3506. The extensionmay produce an audible click or other identifiable sound. In someembodiments, a number of audible clicks (e.g., 1, 2, 3, or more) caninform the user that the electrode system 3508 is fully deployed. Insome embodiments, the detent interaction may be indicative that an eventhas occurred to provide deterministic position, for example longitudinaladvancement of a certain distance (e.g., a cm, an inch, etc.),longitudinal advancement enough to fully deploy the electrode system3508, longitudinal advancement to a rotational movement track, etc. Thesystem 3500 may comprise multiple detents 3520 and/or multiple detentgrooves 3522. In some embodiments, a detent system can inhibit undesiredor accidental movement of the electrode system 3508.

In some embodiments, rotational movement of the knob 3512 or movement ofthe knob 3512 transverse to longitudinal movement can result inrotational movement of the electrode system 3508 in the same rotationalor transverse direction. Twisting and turning of the sheath 3506 mayresult in a movement ratio that is not 1:1. The catheter system 3500 maycomprise a rotational hard stop to limit rotational movement of theelectrode system 3508, for example as described with respect to FIGS.35C and 35D.

FIG. 35C illustrates the catheter system 3500 of FIG. 35A afterlongitudinal advancement and rotation. FIG. 35D is a cross-sectionalview taken along the line 35D-35D of FIG. 35C. Compared to FIG. 35A, theknob 3512 has longitudinally advanced and rotated. The electrode system3508 has also longitudinally advanced and rotated. The rotation of theknob 3512 may be greater than the rotation of the electrode system 3508.In some embodiments, the system 3500 comprises a rotational hard stop3524, for example in the sheath 3506. Even if the knob 3512 was able torotate further in the track groove 3510, the hard stop 3524 wouldinhibit or prevent further rotation of the electrode system 3508. Such asystem can provide a predictable amount of rotational repositioning. Thesystem 3500 may comprise a stop 3516 (e.g., comprising a physicalbarrier) or other means for inhibiting or preventing accidental orunwanted movement of the knob 3512 and/or movement of the electrodesystem 3508.

FIG. 36A is a perspective view of an example of a catheter system 3600.The system 3600 comprises a proximal portion 3602 configured to remainout of the body of a subject and a distal portion 3604 configured to beinserted into vasculature of a subject. The distal portion 3604comprises an expandable structure 3620. The proximal portion comprises ahandle 3610 and an actuation mechanism 3612. The proximal portion 3602is coupled to the distal portion 3604 by a catheter shaft 3606. In someembodiments, the system 3600 comprises a strain relief 3626 between thecatheter shaft 3606 and the expandable structure 3620. The proximalportion 3602 may comprise an adapter comprising a plurality of ports,for example the Y-adapter comprising a first Y-adapter port 3616 and asecond Y-adapter port 3618. The first Y-adapter port 3616 may be incommunication with a lumen configured to allow insertion of a guidewire3615 through the system 3600. The second Y-adapter port 3618 maycomprise an electronics connector 3619, which can be used to couple anelectrode matrix of the system 3600 to a stimulator system.

FIG. 36B is a perspective view of a portion of the catheter system 3600of FIG. 36A in a collapsed state. The illustrated portion includes partof the catheter shaft 3606, the strain relief 3626, and the expandablestructure 3620. The strain relief 3626 may be at least partially in alumen of the catheter shaft 3606. The expandable structure 3620 includesa plurality of splines 3622. Four of the splines 3622 comprise anelectrode array 3624 comprising four electrodes to form a 4×4 electrodematrix. The number of electrodes in the electrode matrix, electrodesizing, electrode spacing, etc. may be in accordance with other systemsdescribed herein. For example, in some embodiments, the expandablestructure 3620 comprises a mesh or membrane comprising electrodes thatis stretched across two or more of the splines 3622. The illustratedportion also includes an actuator wire 3628, which can be coupled to theactuator mechanism 3612 to cause expansion or retraction of theexpandable structure 3620. The actuator wire 3628 may be in a lumen ofthe catheter shaft 3606. A guidewire 3615 is also shown in the lumen ofthe actuator wire 3628. In some embodiments, the actuator wire 3628comprises a lumen capable of receiving a 0.018 inch guidewire 3615.

FIG. 36C is a side view of a portion of the catheter system 3600 of FIG.36A in an expanded state. Operation of the actuation mechanism 3612 cancause the expandable structure 3620 to expand and contract. For example,rotation and/or longitudinal movement of the actuation mechanism 3612can cause the actuator wire 3628 to proximally retract, which can pushthe splines 3622 radially outward. In some embodiments, the distal endsof the splines 3622 are coupled to a distal hub that is coupled to theactuator wire 3628, and the proximal ends of the splines 3622 arecoupled to a proximal hub that is coupled to the catheter shaft 3606. Inthe expanded state, the expandable structure 3620 comprises splines 3622that are spaced from each other generally parallel to a longitudinalaxis at a radially outward position of the splines 3622. The parallelorientation of the splines 3622 can provide circumferential spacing ofthe splines 3622, for example in contrast to singular splines or wiresthat may circumferentially bunch. In some embodiments, the splines 3622comprise wires having a diameter between about 0.006 inches (approx.0.15 mm) and about 0.015 inches (approx. 0.38 mm) (e.g., about 0.006inches (approx. 0.15 mm), about 0.008 inches (approx. 0.2 mm), about0.01 inches (approx. 0.25 mm), about 0.012 inches (approx. 0.3 mm),about 0.015 inches (approx. 0.38 mm), ranges between such values, etc.).A frame comprising openings between arms or splines can help withfixation of the expandable structure 3620. For example, vessel tissuecan deform such that some vessel tissue enters into the openings, whichcan provides a good fixation.

In some embodiments, the diameter 3621 of the expandable structure 3620in the expanded state is between about 15 mm and about 30 mm (e.g.,about 15 mm, about 20 mm, about 22 mm, about 24 mm, about 26 mm, about28 mm, about 30 mm, ranges between such values, etc.). In someembodiments, the splines 3622 may be self-expanding such that theactuation mechanism 3612 or another mechanism (e.g., retraction of asheath over the splines 3622) allows the splines to self-expand from acompressed state for navigation to a target site to an expanded statefor treatment at the target site. In certain such embodiments, thediameter of the expandable structure 3620 in the expanded state may beoversized to most the intended vasculature of most subjects to ensurevessel wall apposition. In some embodiments, the splines 3622 may benon-self-expanding such that the splines only expand upon operation ofthe actuation mechanism 3612. In some embodiments, the splines 3622 maybe self-expanding, and the actuation mechanism 3612 may further expandthe splines 3622, which may provide an adjustable expandable structure3620 diameter usable for a range of vessel sizes, wall appositionforces, etc. Embodiments in which the expandable structure 3620 does notappose the wall in the event of an error could be advantageous forsafety, for example as described with respect to the system 2200. Insome embodiments, the wires are not fixed distally (e.g., to a distalhub), which can allow each wire to move independently, which mayaccommodate curvature at a deployment site. Upon expansion of theexpandable structure 3620, the electrodes of the electrode matrix may beselectively activated for testing nerve capture, calibration, and/ortherapy, for example as described herein.

FIG. 36D schematically illustrates a side view of an example of anexpandable structure 3620. The expandable structure 3620 comprises eightsplines 3622 extending from a proximal hub 3607 to a distal hub 3608.The splines 3622 are grouped in pairs that run generally parallel toeach other. Pairs of the splines 3622 may be different wires or the samewire (e.g., bent at the proximal end or the distal end), for example asdescribed herein. The splines 3622 extend laterally and only outwardlyfrom the proximal hub 3607 at a first angle to the longitudinal axis3671, or parallel to the longitudinal axis 3671 and then bend to formthe first angle after a short length. The splines 3622 continue at thatangle for a first length 3675. In some embodiments, an angle between thelongitudinal axis 3671 and the first length 3675 is between about 10°and about 60° (e.g., about 10°, about 20°, about 30°, about 40°, about50°, about 60°, ranges between such values, etc.).

After the first length 3675, the splines 3622 of each pair of parallelsplines circumferentially diverge at second angles from an axis alignedwith the splines along the first length 3675, coming out of plane withthe longitudinal axis 3671. The second angles may be the same ordifferent. After a short length, the splines 3622 bend again at thirdangles relative to the axis of the first length 3675 to return thesplines 3622 to being parallel with each other. The third angles may bethe same or different. In some embodiments, a difference between thesecond angles and a difference between the third angles arecomplementary. The splines 3622 are parallel for a second length 3676 ata fourth angle with the longitudinal axis 3671, the fourth angle beingabout 0°. In some embodiments, an angle between the first length 3675and the second length 3676 is between about 120° and about 170° (e.g.,about 120°, about 130°, about 140°, about 150°, about 160°, about 170°,ranges between such values, etc.).

After the second length 3676, the splines 3622 bend at fifth anglescoming out of plane with the longitudinal axis 3671 for a short distanceuntil the splines 3622 converge. The fifth angles may be the same ordifferent. In some embodiments, one or both of the fifth angles is thesame as one or both of the third angles. After the splines 3622converge, the splines 3622 bend at seventh angles, which return thesplines 3622 to being parallel with each other and coming into planewith the longitudinal axis 3671 for a third length 3677, still at thefifth angle with respect to the longitudinal axis 3671. In someembodiments, an angle between the longitudinal axis 3671 and the thirdlength 3677 is between about 10° and about 60° (e.g., about 10°, about20°, about 30°, about 40°, about 50°, about 60°, ranges between suchvalues, etc.). In some embodiments, an angle between the third length3677 and the second length 3676 is between about 120° and about 170°(e.g., about 120°, about 130°, about 140°, about 150°, about 160°, about170°, ranges between such values, etc.). The first length 3665 may bethe same as or different from the third length 3667. After the thirdlength 3677, the splines 3622 bend into the distal hub 3608 at the fifthangle or bend to extend into the distal hub 3608 parallel to thelongitudinal axis 3671.

The angles described herein may refer to the shape of the expandablestructure 3620 in the absence of forces. Forces applied by a sheathand/or actuator wire 3628 may increase or decrease the angles. Forexample, restraint of the expandable structure 3620 in a sheath mayreduce the angles of the first length 3675 and the third length 3677relative to the longitudinal axis 3671. For another example,longitudinal extension of the distal hub 3608 relative to the proximalhub 3607 (e.g., by distally advancing the actuator wire 3628) may reducethe angles of the first length 3675 and the third length 3677 relativeto the longitudinal axis 3671. For yet another example, longitudinalretraction of the distal hub 3608 relative to the proximal hub 3607(e.g., by proximally retracting the actuator wire 3628) may increase theangles of the first length 3675 and the third length 3677 relative tothe longitudinal axis 3671.

The area created by the pairs of splines 3622 diverging, being parallel,and then converging, may be a cell. The splines 3622 may compriseelectrodes along at least the second length 3672. This pattern may beproduced using any number of splines 3622. Other bend patterns are alsopossible. For example, the splines 3622 may bend to become parallel withthe longitudinal axis 3671 before diverging and/or remain parallel withthe longitudinal axis 3671 until converging and/or may converge and/ordiverge at a non-parallel angle to the first length 3675 and the secondlength 3677. For another example, the splines 3622 may diverge along thefirst length 3675 and/or converge along the third length 3677. For yetanother example, a single wire may be bent back and forth to form thesplines 3622. For still another example, the bends may be more gentlycurved than angular. The elongated contact between the splines 3622along the second length 3676 and the vessel walls can inhibit or preventwobble of the longitudinal axis 3671 of the expandable structure 3620.In some embodiments, the expandable structure 3620 comprises parallelportions for splines 3622 that comprise electrodes, but splines 3622that do not comprise electrodes, for example splines 3622 that are usedfor vessel wall apposition, may comprise parallel wires, non-parallelwires, wires with other shapes, wires with different diameters,different numbers of wires (e.g., more or fewer), etc. In certain suchembodiments, the expandable structure 3620 may be radially and/orcircumferentially asymmetrical.

FIG. 36E schematically illustrates a side view of another example of anexpandable structure 3630. The portions of the splines 3632 of theexpandable structure 3630 comprising electrodes (e.g., as shown in FIG.36C) are radially inward from an outer diameter in the expanded state.The intersection of the recessed portions and the outer diameter cancreate anchor points 3634, which can help to secure the position of theexpandable structure 3630. In some embodiments, an expandable structure3620 may take the shape of the expandable structure 3630.

FIG. 36F schematically illustrates a side view of still another exampleof an expandable structure 3640. The portions of the splines 3642 of theexpandable structure 3640 comprising electrodes (e.g., as shown in FIG.36C) protrude radially outward or are crowned in the expanded state. Insome embodiments, an expandable structure 3640 may take the shape of theexpandable structure 3620, for example because the generally straightvessel wall may straighten the portions of the splines 3642. A crownedexpandable structure 3640 may counteract forces on an expandablestructure 3620 that may result in the shape of the expandable structure3630 in a vessel, which may increase apposition area and/or reducelongitudinal wobble.

FIG. 36G schematically illustrates a perspective view of yet anotherexample of an expandable structure 3650. The expandable structures 3620,3630, 3640 are illustrated as having splines 3622, 3632, 3642 that areparallel until diverging to form the parallel portions. The expandablestructure 3650 comprises twisted wires 3652 rather than parallel wires,which can make the expandable structure 3650 stiffer while stillproviding some amount of movement as the wires are able to slightlyslide along and around each other. A stiffer expandable structure 3650may help with circumferential spacing of the parallel portions andelectrodes of the electrode matrix. In some embodiments, wires of theexpandable structure 3650 or the expandable structures 3620, 3630, 3640can be coupled (e.g., using a coupling structure), crimped, welded,soldered, adhered, combinations thereof, and the like, which can also oralternatively increase stiffness.

FIG. 36H schematically illustrates an example of an expandable structurepattern. The pattern is also illustrated in the expandable structures3620, 3630, 3640, and includes parallel portions having proximalstarting and distal ending points that are generally circumferentiallyaligned. Circumferential alignment may reduce manufacturing complexity,for example because the expandable structure 3620 is symmetrical so thesame tooling and setup may be used to shape each wire. Circumferentialalignment may provide electrode matrix flexibility, for example if eachof the splines comprises the same electrode array such that anyrotational position is acceptable.

FIG. 36I schematically illustrates another example of an expandablestructure pattern. The middle parallel portions have proximal startingand distal ending points that are shifted distally from the proximalstarting and distal ending points, respectively, of the top and bottomparallel portions. Staggering the starting and/or ending points canallow the splines to nest in a collapsed state, which can reduce systemdiameter. Staggering the starting and/or ending points can reduce thechances that an electrode may snag during expansion and/or collapse ofthe expandable structure.

FIG. 36J schematically illustrates another example of an expandablestructure pattern. The middle parallel portions have proximal startingpoints that are shifted proximally and distal ending points that areshifted distally from the proximal starting and distal ending points,respectively, of the top and bottom parallel portions. Staggering thestarting and/or ending points can allow the splines to nest in acollapsed state, which can reduce system diameter. Staggering thestarting and/or ending points can reduce the chances that an electrodemay snag during expansion and/or collapse of the expandable structure.

FIG. 36K schematically illustrates another example of an expandablestructure pattern. The wires includes parallel portions as in theexpandable structures 3620, 3630, 3640, and the portions of the wiresproximal and distal to the parallel portions do not circumferentiallyconverge for each set of parallel portions. Wires that do not convergeor wires that converge less or partially (e.g., at one end of each setof parallel portions) can reduce forces (e.g., rotational or twistingforces) that may otherwise cause uneven spacing of the parallel portionsin an expanded state.

FIG. 36L schematically illustrates another example of an expandablestructure pattern. The parallel portions comprise a third non-divergingspline between the diverging parallel portions. In embodiments in whicheach of the splines includes electrodes, a third spline can increase thenumber of rows in an electrode matrix and/or provide more flexibility inelectrode positioning. More or fewer wires or splines are also possible.Some or all of the wires or splines may include electrodes and/or may becoupled to a membrane or mesh comprising electrodes.

FIG. 36M schematically illustrates another example of an expandablestructure pattern. As opposed to comprising a plurality of wires, thesplines comprise flat surfaces of a cut hypotube. In some embodiments, aplurality of electrodes is positioned on an outer side of one or moresplines. A wide variety of cut patterns are possible. For example,splines comprising electrodes may be shaped to correspond to theelectrode shapes and/or pattern. In some embodiments, the splines maycomprise flat wires (e.g., having a rectangular cross-section). In someembodiments, the splines may comprise U-shaped wires (e.g., as describedherein.

FIG. 36N schematically illustrates an example of an expandablestructure. The expandable structure comprises a mesh 3660 coupled to thesplines. The mesh 3660 may comprise an electrode matrix in accordancewith the disclosure herein. In some embodiments, a first circumferentialedge of the mesh 3660 may be coupled to a first spline and a secondcircumferential edge of the mesh 3660 may be coupled to a second splinesuch that the remainder of the mesh can slide with respect to othersplines.

FIG. 36O schematically illustrates an example of an expandable structurepattern. The splines comprise a sinusoidal or wave or undulating orzig-sag shape. The undulating wires may provide more flexibility inelectrode positioning. For example, electrodes may be placed at peaks,troughs, and/or rising or falling portions. The undulating wires mayprovide better wall apposition than parallel portions due to moresurface area contact with the vessel wall.

FIG. 36P schematically illustrates a side view of an example of anexpandable structure 3660. FIG. 36Q is a proximal end view of theexpandable structure 3660 of FIG. 36P. The expandable structure 3660comprises ten splines 3662 extending from a proximal hub 3663 to adistal hub 3664. The splines 3662 are grouped in pairs that rungenerally parallel to each other. Pairs of the splines 3662 may bedifferent wires or the same wire (e.g., bent at the proximal end or thedistal end), for example as described herein. The splines 3622 may eachhave a proximal starting point and distal ending point that are notcircumferentially aligned. The splines 3662 extend from the proximal hub3663 at a first angle to the longitudinal axis 3661, or straight andthen bend to the first angle after a short length. The splinessimultaneously extend in a circumferential direction at a second anglerelative to a circumferential origin. The splines 3662 continue at thoseangles for a first length 3665. After the first length 3665, half of thesplines 3662, one from each pair of parallel splines 3662, bends in acircumferential direction at a third angle greater than the secondangle, and the other half of the splines 3662, the other from each pairof parallel splines 3662, bends at a fourth angle opposite the secondangle. These bends cause the pairs of splines 3662 to circumferentiallydiverge.

After a short length, the splines 3622 bend again, at a fifth angle anda sixth angle, so that the pairs of splines 3662 are parallel to eachother, at a seventh angle 3668 relative to the longitudinal axis 3661,for a second length 3666. The second length 3666 may be the same as ordifferent than (e.g., greater than) the first length 3665. The seventhangle 3668 may be the same as or different than the first angle. Theseventh angle 3668 may be between about 5° and about 60° (e.g., about5°, about 10°, about 15°, about 20°, about 25°, about 30°, about 35°,about 40°, about 45°, about 50°, about 55°, about 60°, ranges betweensuch values, etc.). After the second length 3666, the splines 3662 againbend in opposite circumferential directions, at an eight angle and anninth angle opposite to the seventh angle, to circumferentially convergeat a tenth angle relative to the longitudinal axis 3661. The areascreated by the pairs of splines 3662 diverging, being parallel, and thenconverging, may be a cell. The splines 3662 may comprise electrodesalong at least the second length 3666. The tenth angle may be the sameor different as the first angle. After a short length, the splines 3662bend again, at an eleventh angle and a twelfth angle, so that the pairsof splines 3662 are again parallel to each other, at the tenth anglerelative to the longitudinal axis 3661 and a thirteenth angle relativeto the circumferential origin, for a third length 3667. The third length3667 may be the same as or different than the first length 3665. Thesecond length 3666 may be the same as or different than (e.g., lessthan) the second length 3666. In the embodiment illustrated in FIG. 36P,the first length 3665 is about the same as the third length 3667, andthe second length 3666 is greater than each of the first length 3665 andthe third length 3667. The thirteenth angle may be the same as ordifferent than the seventh angle. The thirteenth angle may be the sameas or different than the second angle. The splines 3662 extend intodistal hub 3664 at the tenth angle relative to the longitudinal axis3661 and the thirteenth angle relative to the circumferential origin, orbend to extend straight into the distal hub 3664.

The starting proximal point and distal ending point for each spline 3622may be circumferentially offset, for example depending on the bendangles and lengths. This pattern may be produced using any number ofsplines 3662. Splines 3662 at an angle to the longitudinal axis 3661 mayprovide better wall apposition than splines that extend parallel to thelongitudinal axis, for example due to increased surface area contactwith the vessel wall. Although the expandable structure 3660 may beconsidered an angled, 5-pair version of the expandable structure 3620,for example, any of the expandable structures described herein may beangled as appropriate. In some embodiments, the splines 3662 may beshape set to be angled. In some embodiments, the splines 3662 may beangled during use, for example by rotating the distal hub 3664 relativeto the proximal hub 3663.

Combinations of the expandable structure patterns described herein andother expandable structure patterns are also possible. For example, anexpandable structure may comprise longitudinal offset and three wires.For another example, an expandable structure may comprise longitudinaloffset and undulating wires. In some embodiments, an anchor (e.g., barb)may be integrated with splines of an expandable structure.

FIG. 37A is a perspective view of an example of catheter system 3700.The catheter system 3700 may share at least some similar features withthe catheter system 3600 and/or other catheter systems described herein.The system 3700 comprises a proximal portion 3702 configured to remainout of the body of a subject and a distal portion 3704 configured to beinserted into vasculature of a subject. The distal portion 3704comprises an expandable structure 3720. The proximal portion comprises ahandle 3710. A catheter shaft assembly 3706 extends from the handle 3710to the proximal end of the expandable structure 3720. An actuation tube3728 extends from the handle 3710 through the catheter shaft assembly3706 to the distal end of the expandable structure 3720. The proximalend 3702 further comprises an electrical socket 3799, which isconfigured to connect to an electrical plug of a neurostimulator (e.g.,radiofrequency generator or other appropriate source depending on thestimulation or ablation modality).

FIG. 37B schematically illustrates a side view of expandable structure3720 and FIG. 37C shows a proximal end view of expandable structure3720. The expandable structure 3720 includes a plurality of splines 3722extending from a proximal hub 3740 to a distal hub 3750. Some splines3722 of the expandable structure 3720 may include electrodes 3724configured to stimulate a target nerve. Some of the splines 3722 may bedevoid of, free from, or not include electrodes 3724. In someembodiments, the expandable structure 3720 includes ten splines 3722, ofwhich four circumferentially adjacent splines 3722 each comprise fiveelectrodes 3724. The splines 3722 may comprise proximal segments,intermediate segments, and distal segments. The intermediate segmentsmay be configured to extend radially outward when the expandablestructure 3720 is in a self-expanded state. The proximal segment of aspline 3722 may form a first angle with the intermediate segment and thedistal segment may form a second angle with the intermediate segment. Insome embodiments, the proximal segment and distal segment may bestraight and the intermediate segment may be convex, bending radiallyoutward. In some embodiments, the proximal segment and distal segmentmay be straight and the intermediate segment may be concave, bendingradially inward. In some embodiments, the proximal segment, intermediatesegment, and distal segment may all be straight. Splines 3722 whichcomprise electrodes 3724 may comprise proximal segments and distalsegments devoid of electrodes 3724. The splines 3722 may furthercomprise proximal transitional segments, joining the proximal segmentsand intermediate segments, and distal transitional segments, joining theintermediate segments and distal segments.

The splines 3722 comprising electrodes 3724 may be configured to extendoutwardly on one side of a plane crossing a longitudinal axis of theexpandable structure 3720. The splines 3722 not comprising electrodes3724 may be configured to extend outwardly on a second side of the planeopposite the one side. For example, the splines 3722 not comprisingelectrodes 3724 illustrated in FIG. 37C could be less circumferentiallyspaced to be on the same side of a plane crossing the longitudinal axisat the center of the expandable structure 3720. The splines 3722comprising electrodes 3724 may circumferentially occupy less than 180°on the one side. For example, the splines 3722 comprising electrodes3724 may circumferentially occupy about 30° to about 170° (e.g., about30°, about 45°, about 60°, about 90°, about 100°, about 110°, about120°, about 150°, about 170°, ranges between such values, etc.). Thefour splines 3722 comprising electrodes 3724 illustrated in FIG. 37Ccircumferentially occupy about 110°.

Other numbers of splines 3722 comprising electrodes 3724 are alsopossible. For example, all of the splines 3722 or a subset of thesplines 3722 (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 of the splines3722) may comprise an electrode 3724. In embodiments comprising morethan 10 splines, more than 10 splines may comprise an electrode. All ofthe splines 3722 or a percentage of the splines 3722 (e.g., 10%, 20%,30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% of the splines 3722) maycomprise an electrode 3724. The splines 3722 that comprise an electrode3724 may be circumferentially adjacent or have one or more non-electrodesplines 3722 therebetween.

The splines 3722 may comprise between one electrode 3724 and twentyelectrodes 3724 (e.g., 1 electrode, 2 electrodes, 3 electrodes, 4electrodes, 5 electrodes, 6 electrodes, 7 electrodes, 8 electrodes, 9electrodes, 10 electrodes, 15 electrodes, 20 electrodes, ranges betweensuch values, etc.). More electrodes 3724 can provide more stimulationoptions and/or more targeted nerve capture. Fewer electrodes 3724 canreduce the number of electrical connectors, which can reduce deviceprofile and/or reduce valuable device volume taken by electricalconnectors.

FIG. 37D is a perspective view of a wire bent to form a spline pair3727. A single wire may be bent at a bend 3725 to form a spline pair3727 comprising a first spline 3722A from a first portion of the wireand a second spline 3722B from a second portion of the wire. The bend3725 may be positioned at the proximal end of the spline pair 3727, suchthat a proximal-facing end of the spline pair 3727 is an atraumatic bendas opposed to possibly traumatic wire ends. The bend 3725 may bepositioned at the distal end of the spline pair 3727. The spline pair3727 may be formed with two or more individual wires positioned in thesame configuration, for example coupled by welding, soldering, etc. Thesplines 3722A, 3722B may each comprise a different wire. The wires maybe coupled, for example at a proximal end, or not coupled. One or bothends of the wires may be bent to be atraumatic. The spline pair 3727 maybe shaped with two generally parallel splines 3722 which run alongsideeach other at their proximal and distal ends (e.g., along proximal anddistal segments) but are separated by a greater distance along a centralportion (e.g., an intermediate segment). As best seen in FIG. 37C, thesplines 3722 circumferentially diverge at the beginning and end of acentral portion of the spline 3722 (e.g., along proximal transitionalsegments and distal transitional segments) as they continue to extendradially outward. The convergence and divergence of the splines 3722forms two short lengths during which the splines 3722 in a spline pair3727 are not parallel. The splines 3722 of a spline pair 3727 runparallel within their central portions to form a generally hexagonalshape. The splines 3722 may share features with any of the patterns orconfigurations of expandable structures disclosed herein or variationsthereof. As non-limiting examples, the central portions of the splines3722 may be substantially parallel to the longitudinal axis of theexpandable structure 3720, for example as shown in FIG. 36H, curveradially inward, for example as shown in FIG. 36E, radially outward, forexample as shown in FIG. 36F, and/or have other configurations.

Some splines 3722 of the expandable structure 3720 may not include orlack or be devoid of or be free of electrodes 3724. After inserting thesplines 3722 without electrodes 3724 through the proximal hub 3740, thesplines 3722 may be wrapped with heat shrink tubing 3721, for examplealong their parallel and adjacent proximal and distal portions. The heatshrink tubing 3721 is then shrunk by heating. The heat shrink tubing3721 may comprise, for example, polyethylene terephthalate (PET) oranother suitable material. The heat shrink tubing 3721 can help inhibitrotation of the wrapped portions of the splines 3722 of a spline pair3727 relative to each other. If the expandable structure 3720 isretracted through the pulmonary valve in an expanded state, the heatshrink tubing 3721 along the proximal portion of the splines 3722 mayprovide a more favorable proximally-facing surface than the splines 3722for interaction with the valve tissue.

The wires forming the splines 3722 may be formed from a shape memoryalloy such as Nitinol. In such cases, the wires are heated andprogrammed into a desired memory shape, such as the configurationdepicted in FIG. 37D, then rapidly cooled. The wires may then bedeformed as needed and inserted through the spline lumens 3745 and willreturn to their predetermined memory shape upon heating above atransition temperature. Once the wire is threaded through two adjacentspline lumens 3745 and returned to its programmed conformation,including the spline bend 3725 in the wire, the spline pair 3727 may bepulled distally until the spline bend snaps into place within a recess3747 behind a proximal hub step 3748 (FIG. 37G).

FIG. 37E is a perspective view of a spline pair 3727. The spline pair3727 comprises five electrodes 3724 positioned across the centralportion of each splines 3722A, 3722B. The two splines 3722A, 3722B of asingle spline pair 3727 may each comprise an electrode 3724, may each bedevoid of electrodes 3724, or one of the splines 3722A, 3722B maycomprise an electrode 3724 while the other of the splines 3722A, 3722Bis devoid of electrodes.

FIG. 37F is an expanded view of the distal end of the spline pair 3727of FIG. 37E. The splines 3722 comprising an electrode 3724 may be atleast partially covered by a lining 3729, for example not at theproximal end and/or distal end. The lining 3729 may comprise PTFE. Inembodiments in which the inner surfaces of the electrodes 3724 are notinsulated, the lining 3729 may electrically insulate the splines 3722from the electrodes 3724, which can inhibit cross-talk, activation ofunintended electrodes, inefficient operation due to electrical leakage,etc. In embodiments in which the inner surfaces of the electrodes 3724are insulated or other circumstances, the lining 3729 may be omitted.The splines 3722 not comprising an electrode 3724 may be free of alining 3729, for example to provide better vessel wall apposition thatis not prone to sliding. After inserting the splines 3722 through theproximal hub 3740, which may be before or after lining, lined splinewires may be wrapped with a spline tube 3723 that joins the two splines3722A, 3722B of a spline pair 3727 at their proximal and distal ends.The spline tube 3723 may comprise two adjacent, yet, distinct lumens foreach spline 3722 or it may comprise a single (e.g., oblong) lumen at itsproximal and distal ends for receiving both splines. The spline tube3723 may split at the proximal and distal points where the splines3722A, 3722B diverge and cover each spline 3722A, 3722B individuallyalong its central portion, such that the spline tube 3723 has twoY-shaped ends. Being spaced at the central portion of a spline pair 3727may reduce the risk of thrombosis and/or provide better wall appositionby allowing the splines 3722 to abut the wall at circumferential points.The spline tube 3723 may span the expanse between the central portionsof the splines 3722, which may provide a wider variety of electrode 3724configurations (e.g., as described with respect to FIG. 4C) and/orprovide better wall apposition by providing more apposition surfacearea. A plurality of spline tubes 3723 may be used, for example, onespline tube 3723 for each spline 3722. Spline tubes 3723 may optionallybe coupled, for example at proximal and distal portions of a spline pair3727. Spline tubes 3723 may be sized to be touching but not coupled. Thespline tube 3723 may inhibit rotation of splines 3722A, 3722B of aspline pair 3727 relative to each other.

The individual electrodes 3724 may be generally cylindrical surroundingthe circumference of central portions of the splines 3722. Other typesand configurations of electrodes 3724 are also possible. For example,the electrodes 3724 may extend only partially around the circumferenceof the splines 3722 such that they face the outer diameter of theexpandable structure 3720 (e.g., as described with respect to theelectrode 4403).

The expandable structure 3720 may comprise five spline pairs 3727 spacedabout the circumference of the expandable structure. The spline pairs3727 may be evenly circumferentially spaced (e.g., as shown in FIG.37C). Some of the spline pairs 3727 may be circumferentially clustered.For example, spline pairs 3727 comprising electrodes 3724 may be on afirst side of a plane intersecting the longitudinal axis and splinepairs without electrodes 3724 may be on a second side of the planeopposite the first side. Two circumferentially adjacent spline pairs3727 may each comprise a set of electrodes 3724, such as five electrodes3724 per spline 3722, to form a 4×5 array of twenty electrodes 3724.

FIGS. 37Fi-37Fiii illustrate an example of electrical movement ofelectrodes. The expandable structure 3720, or other expandable membersdescribed herein, is expanded in a vessel. The electrodes may beselectively activated, for example as described herein, to determine acombination that stimulates the target nerve. In FIG. 37Fi, twoelectrodes in the first column have been found to capture a target nervewhen activated. After some duration of treatment, stimulation of thetarget nerve may not be as effective as during the original selection.One option would be to contract, reposition, and reexpand the expandablestructure 3720, and then repeat the selective activation process.Another non-mutually exclusive option is to electrically move theexpandable structure 3720 to better capture the target nerve. In FIG.37Fii, two electrodes in the fourth column have been found to capturethe target nerve when activated. Changing the stimulation from theelectrodes in the first column to the electrodes in the fourth columneffectively moves or longitudinally shifts the expandable structure 3720by the distance 3701. In FIG. 37Fiii, two electrodes in the first columnbut in the second and third rows have been found to capture the targetnerve when activated. Changing the stimulation to these electrodeseffectively circumferentially rotates the expandable structure 3720 bythe distance 3703. Combinations of effective longitudinal movement andcircumferential rotation are also possible. Although illustrated asbipolar operation in which two electrodes have opposite charges,monopolar operation (e.g., stimulation of one or more electrodes withthe same charge in combination with a return electrode that is not anelectrode of the electrode array (e.g., a chest pad, on a proximalportion of the catheter system 3700, on a separate catheter, etc.) isalso possible. Although illustrated as simple bipolar operation for easeof explanation, guarded bipolar operation and other techniques are alsocompatible with electrical movement. Factors that may affect theprecision with which an electrode array can capture a target nerve mayinclude the total number of electrodes 3724, the span and shape of anelectrode array, the proportioning of electrodes 3724 on individualsplines 3722, the spacing of electrodes 3724 across the lengths of thesplines 3722, and the circumferential spacing of the splines 3722, etc.An electrode array configured to allow electrical movement mayadvantageously reduce or eliminate physical or mechanical repositioningthe expandable structure 3720, which could include contracting, moving,and reexpanding the expandable structure 3720. Physical movement cancause adverse events such as ischemic stroke (e.g., by causing debris tofloat loose or promoting thrombosis), damage to the vessel wall (e.g.,promoting stenosis), etc. Physical movement can be time consuming,during which the subject may not be being treated.

Referring again to FIG. 37B, the expandable structure 3720 comprises aproximal hub 3740 and distal hub 3750 from which the splines 3722extend. The proximal hub 3740 may comprise stainless steel or anothersuitable material. The distal hub 3750 may comprise stainless steel oranother suitable material. The proximal hub 3740 and the distal hub 3750may comprise the same material or different materials.

FIG. 37G is a perspective view of an example of a proximal hub 3740 ofan expandable structure (e.g., the expandable structure 3720). FIG. 37Hschematically illustrates a side cross-sectional view of the proximalhub 3740 of FIG. 37G. The proximal hub 3740 may comprise a biocompatiblematerial such as, for example, stainless steel, nitinol, plastic, etc.The proximal hub 3740 may comprise a proximal portion 3741 and a distalportion 3742. The distal portion 3742 has a larger diameter than theproximal portion 3741 and may taper at its distal end to form apartially rounded surface 3749. A central lumen 3743 extends throughboth the proximal portion 3741 and the distal portion 3742, providing achannel from the proximal end of the proximal hub 3740 to the distal endof the proximal hub 3740 through which an actuation tube 3728 mayslidingly extend. Although illustrated as having a circularcross-section, the central lumen 3743 may have other cross-sectionalshapes (e.g., oval, arcuate, polygonal, etc.). The central lumen 3743may include a lubricious coating or liner (e.g., comprising PTFE).

The proximal portion 3741 may be radially inward of the distal portion3742. In some embodiments, a difference in diameter or outer dimensionof the proximal portion 3741 and the distal portion 3742 may beapproximately the thickness of a hinge 3726, which can allow theproximal hub 3740 to be coupled to a hinge 3726 while maintaining auniform outer sheath 3711 (FIG. 37O) diameter if the outer sheath 3711overlaps the distal portion 3742. In some embodiments, a difference indiameter or outer dimension of the proximal portion 3741 and the distalportion 3742 may be approximately the thickness of a hinge 3726 plus thethickness of an outer sheath 3711, which can allow the proximal hub 3740to be coupled to a hinge 3726 while maintaining a uniform diameter ifthe outer sheath 3711 abuts the distal portion 3742. Other differencesmay be appropriate for other types of catheter shafts, for example notincluding a hinge 3711.

A plurality of peripheral lumens 3744 extends through both the proximalportion 3741 and distal portion 3742, providing a plurality ofperipheral channels from the proximal end of the proximal hub 3740 tothe distal end of proximal hub 3740 through which electrical connectorsmay extend and/or through which fluid may flow. The peripheral lumens3744 may be radially outward of the central lumen 3743. The peripherallumens 3744 may have a smaller diameter than the central lumen 3743. Theperipheral lumens 3744 may each have the same diameter or at least oneof the peripheral lumens 3744 may have a different diameter. Althoughillustrated as having a circular cross-section, the peripheral lumens3744 may have other cross-sectional shapes (e.g., oval, arcuate,polygonal, etc.). The peripheral lumens 3744 may each have the sameshape or at least one of the peripheral lumens 374 may have a differentshape. For example, peripheral lumens 3744 configured for an electricalconnector to extend therethorugh may have one diameter or shape andperipheral lumens 3744 configured to deliver fluid may have anotherdiameter or shape. Although the proximal hub 3740 is illustrated ashaving five peripheral lumens 3744, other quantities of peripherallumens 3744 are also possible. For example, the proximal hub 3740 mayinclude at least one peripheral lumen 3744 per spline pair 3727, atleast one peripheral lumen 3744 per spline 3722, at least one peripherallumen 3744 per spline 3722 comprising an electrode, at least oneperipheral lumen 3744 per spline pair 3727 comprising an electrode, atleast one peripheral lumen 3744 per electrical connector, etc. Althoughthe proximal hub 3740 is illustrated as having five peripheral lumens3744 equally spaced about the circumference of the proximal hub 3740,other arrangements of the peripheral lumens 3744 are also possible. Someperipheral lumens 3744 may be circumferentially bunched or grouped orclustered. For example, peripheral lumens 3744 configured for anelectrical connector to extend therethrough may be circumferentiallyclustered and peripheral lumens 3744 configured to deliver fluid may besubstantially equally circumferentially spaced about the remainder ofthe proximal hub 3740. A proximal hub 3740 comprising peripheral lumens3744 that each have the same size, shape, and spacing may providemanufacturing flexibility and/or adaptability to a variety of designs. Aproximal hub 3740 comprising at least one peripheral lumen 3744 having adifferent size, shape, and/or spacing may provide enhanced performancefor a type of design.

The distal portion 3742 of the proximal hub 3740 may comprise splinelumens 3745. One or more splines 3722 may be positioned in each splinelumen 3745. In an example method of manufacture, a wire may be bent, forexample as shown in FIG. 37D. The free ends of the wire may be insertedinto the proximal ends of the spline lumens 3745 and then advanceddistally until the bend 3725 contacts or is proximate to the proximalend of the distal portion 3742 of the proximal hub 3740. The bend 3725in each spline pair 3727 can inhibit or prevent the spline pair 3727from sliding distally because it contacts the proximal end of the distalportion 3742 of the proximal hub 3740.

The proximal portion 3741 may include recesses 3747 configured toaccommodate or receive portions of splines 3722 extending proximal tothe proximal end of the distal portion 3742 of the proximal hub 3740.The portions of the splines 3722 may comprise the bends 3725. Theportions of the splines 3722 may comprise the free ends of the splines3722, which may optionally be bent, for example to an atraumatic shape.If the recesses 3747 are flattened portions of an otherwise arcuateproximal portion 3741, the segment between the recesses 3747 and theradially outward surface may form steps 3748. The proximal portion 3740may comprise one recess 3747 and one step 3748 per spline pair 3727. Theproximal portion 3740 may comprise one recess 3747 and one step 3748 pertwo splines 3722, whether or not in a spline pair 3727. The proximalportion 3740 may comprise one recess 3747 and one step 3748 per spline3722. The proximal portion 3740 may comprise one arcuate recess 3747around or substantially around the circumference of the proximal portion3740. The proximal portion 3740 may comprise one or more arcuaterecesses 3747 for splines 3722 comprising an electrode 3724 and one ormore recesses 3747 for splines 3722 lacking an electrode 3724.

The steps 3748 may limit the proximal motion of the proximal ends of thesplines 3722. In implementations comprising a bend 3725, if the splines3722 came out of the recesses 3747, then the surfaces that mightinteract with a vessel wall during retraction of an expandable structure3720 comprising the splines 3722 and proximal hub 3740 would beatraumatic, and thus may not be prone to puncturing or otherwiseadversely affecting the vessel. If the distal ends of the splines 3722were straight wires and came out of the distal hub 3750, then thesurfaces that might interact with a vessel wall during proximalretraction would be facing distally, the direction opposite retraction,and thus may not be prone to puncturing or otherwise adversely affectingthe vessel. If the splines 3722 of the expandable structure 3720 have aportion that is bent radially outward, then the proximal and distal endsof the splines 3722 may be biased to be radially inward of an outwardsurface, and thus may not be prone to puncturing or otherwise adverselyaffecting the vessel.

The splines 3722 may be slidingly engaged with the spline lumens 3745.Upon proximal retraction of an actuation tube 3728, the steps 3748 mayprovide a counter force against the proximal ends of the splines 3722,forcing the splines 3722 to bend radially outward. The radially outwardconfiguration may be different, for example, than an expandedconfiguration provided by shape memory. The splines 3722 may be fixablycoupled to the spline lumens 3745. In certain such implementations, theinteraction between the splines 3722 and the spline lumens 3745,independent of recesses 3747, steps 3748, and/or the proximal end of thedistal section 3742 of the proximal hub 3740, can inhibit proximal anddistal motion of the splines 3722 relative to the hub 3740. In someembodiments, friction between the splines 3722 and the spline lumens3745 may provide additional or alternative counter force. The bends 3725in the spline pairs 3727 form atraumatic proximal ends, which can beless dangerous to vasculature in a device failure scenario that resultsin the proximal ends of the splines 3722 coming free or misaligned suchthat they inadvertently contact the walls of the blood vessel. Thespline pairs 3727 may be formed from individual wires or wirescomprising a bend at their distal ends. In certain such embodiments, thesplines 3722 may comprise a proximal bend or loop, the splines 3722 maybe fixably coupled to the spline lumens 3745, and/or the splines lumens3755 may comprise channels that are closed off at their proximal ends.The distal end of the distal portion 3742 of the proximal hub 3740 maybe tapered such that the distal end of spline lumens 3745 open at anangle to a rounded surface 3749. The angled open ends of the splinelumens 3745 at their distal ends may allow the splines 3722 to moreeasily bend radially outward, which may reduce stress on the wire whenadopting an expanded configuration.

FIG. 37I is a perspective view of a distal end of the proximal hub 3740of FIG. 37G. The wires or leads or conductors 3712 connecting theelectrodes 3724 to the electrical socket 3799 may extend through theperipheral lumens 3744 of the proximal hub 3740. As illustrated in FIG.37I, the conductors 3712 may be apportioned between the peripherallumens 3744 such that the conductors 3712 for all of the electrodes ofone or more splines 3722 extend through the same peripheral lumen 3744.For example, if the expandable structure 3720 comprises two adjacentspline pairs 3727 each comprising five electrodes 3724, the fiveconductors 3712A connected to the electrodes 3724 of a first spline 3722may extend through a first peripheral lumen 3744A, the five conductors3712B connected to the electrodes 3724 of a second spline 3722 in aspline pair 3727 with the first spline 3722 may extend through a secondperipheral lumen 3744B, the five conductors 3712C connected to theelectrodes 3724 of a third spline 3722 may extend through the secondperipheral lumen 3744B, and the five conductors 3712D connected to theelectrodes 3724 of a fourth spline 3722 in a spline pair 3727 with thethird spline 3722 may extend through a third peripheral lumen 3744C. Afourth peripheral lumen 3744D and a fifth peripheral lumen 3744E may befree of conductors 3712. Other distributions of conductors 3712 inperipheral lumens 3744 are also possible. For another example, all ofthe conductors 3712 may extend through one peripheral lumen 3744. Foryet another example, all of the conductors 3712 for each spline 3722 mayextend through one peripheral lumen 3744 that is different for eachspline 3722. For still another example, all of the conductors 3712 fortwo splines 3722 (e.g., in a spline pair 3727) may extend through oneperipheral lumen 3744. A peripheral lumen 3744 free from conductors 3712may be circumferentially between two peripheral lumens 3744 withconductors 3712 extending therethrough. Fluid flow through a peripherallumen 3744 may be inversely proportional to the number of conductors3712 occupying the peripheral lumen 3744, such that more fluid flowsthrough peripheral lumens 3744 with fewer conductors 3712. Fluid flowthrough the device 3700 is described in further detail herein.

FIG. 37J schematically illustrates a side cross-sectional view of anexample of a distal hub 3750 of an expandable structure (e.g., theexpandable structure 3720). The distal hub 3750 may comprise abiocompatible material such as, for example, stainless steel, nitinol,plastic, etc. The distal ends of splines 3722 extend into the distal hub3750. The distal hub 3750 may be generally cylindrical in shape, and mayinclude an atraumatic (e.g., rounded) distal end 3754 and/or a taperedproximal end 3756. The tapered end 3756 may create angled open faces onthe proximal end of the channels 3755 which allow the inserted splines3722 to more easily bend in achieving an expanded configuration. Thedistal hub 3750 may comprise a central lumen 3753 configured to receivean actuator tube 3728. The actuator tube 3728 may be inserted into orthrough the central lumen 3753 and fixably coupled to the distal lumen3753 by any suitable means, such as adhesive (e.g., cyanoacrylate),welding, soldering, combinations thereof, etc. The distal hub 3750comprises a plurality of recesses 3755 configured to receive the distalends of the splines 3722. A recess 3755 may have the same shape as thedistal end of a spline 3722, for example being elongate and cylindrical.The distal hub 3750 may comprise a plurality of recesses 3755 eachconfigured to receive the distal end of one spline 3722. The splines3722 may be rigidly affixed to the distal hub 3750 by welding the distalhub 3750 after the distal ends of the splines 3722 are inserted into therecesses 3755. Welding may comprise applying a heat source around (e.g.,360° around) the outer circumference of the distal hub 3750. Welding maycomprise using a laser and/or another suitable heat source. The splines3722 may be welded to the distal hub 3750. Welding the outercircumference of the distal hub 3750 may, with or without welding thesplines, heat stake the splines 3722 in the recesses 3755 by deformablyreducing the inner diameters of the recesses 3755.

The actuation tube 3728 slidingly extends through the central lumen 3743of the proximal hub 3740, then through a radially inner portion (e.g.,the center) of the expandable structure 3720, then is fixably coupled tothe central lumen 3753 of the distal hub 3750. The distal end of theactuation tube 3728 may be coupled to distal hub 3750 by any suitablemeans, such as adhesive (e.g., cyanoacrylate), welding, soldering,combinations thereof, etc. When the actuation tube 3728 is proximallyretracted, the actuation tube 3728 proximally pulls the distal hub 3750toward the proximal hub 3740, which is held in place by the cathetershaft assembly 3706. As the proximal hub 3740 and distal hub 3750 arebrought closer together, the compressive force on the expandablestructure 3720 forces the splines 3722 to expand radially outwardly,increasing the diameter and/or reducing the length of the expandablestructure 3720. The diameter of the expandable structure may be greaterthan a shape set expanded shape of the expandable structure 3720. Whenthe actuation tube 3728 is distally advanced, the actuation tube 3728distally pushes the distal hub 3750 away from the proximal hub 3740,which is held in place by the catheter shaft assembly 3706. As theproximal hub 3740 and distal hub 3750 are brought further apart, theexpansion force on the expandable structure 3720 forces the splines 3722to retract radially inwardly, decreasing the diameter and/or increasingthe length of the expandable structure 3720.

FIG. 37K shows a side view of an example of a proximal end 3702 of thecatheter system 3700 of FIG. 37A. The proximal end 3702 comprises ahandle 3710 and a portion of a catheter shaft assembly 3706 extendingtherefrom. The handle 3710 is configured to remain outside the body. Thehandle 3710 comprises a proximal part 3761 and a distal part 3762movable relative to the proximal part 3761. The distal part 3762 maycomprise a handle base 3763 and an outer handle 3770. The outer handle3770 may include a grip portion (e.g., comprising a textured surface),which can enhance friction to provide better user grip. The proximalpart 3761 may comprise an actuator 3780 and a hemostasis valve 3784. Theproximal part 3761 and the distal part 3762 may be movably coupled by anactuation tube assembly 3790 and a securing member 3774 comprising alocking member 3776. Electrical conductors 3712 configured to supplysignals to the electrodes 3724 may enter the handle 3710 via connectortubing 3798, which joins the handle 3710 to an electrical socket 3799.The outer handle 3770 may include a projection 3771 with a guide portthrough which the connector tubing 3798 may travel such that theconnector tubing 3798 is secured along the side of the distal part 3762of the handle 3710. The handle 3710 may be asymmetric with respect tothe longitudinal axis of the catheter shaft assembly 3706, which canassist a user in approximating the amount of twisting or rotation in theattached catheter shaft assembly 3706.

FIG. 37L is a side cross-sectional view of the proximal end 3702 of FIG.37K. The outer handle 3770 comprises a recess extending distally fromits distal end that is configured to receive the handle base 3763. Theproximal portion of the handle base 3763 may be partially inserted intothe recess and fixably coupled to the handle base 3763.

The outer handle 3770 comprises a first lumen 3772 configured toslidably receive a portion of the actuation tube assembly 3790. Theouter handle 3770 may include a second lumen 3773 configured to receivea securing member 3774 such as a pin, screw, piston, etc. The securingmember 3774 may comprise, for example, a socket head cap screwcomprising a threaded elongate section and a cap 3775. If the securingmember 3774 is fixably coupled to the actuator 3780, the lumen 3773 maybe devoid of threads so that the securing member 3774 may longitudinallyslide through the lumen 3773. The threaded elongate section may interactwith complementary threads in a lumen of the locking member 3776. If thesecuring member 3774 is rotatably coupled to the actuator 3780, thelumen 3773 may comprise complementary threads, and securing member 3774may longitudinally slide through the lumen 3773 while rotating. Theouter handle 3770 may comprise a shoulder extending into the secondlumen 3773 configured to interact with an enlarged portion of thesecuring member 3774. For example, the shoulder may inhibit or preventproximal retraction of the cap 3775, and thus the securing member 3774,beyond a certain length. Limiting longitudinal translation of thesecuring member 3774, which is fixably coupled to the actuator 3780,which is fixably coupled to the actuation tube 3728, can limit radialexpansion of the expandable member 3720. Limiting radial expansion ofthe expandable member 3720 can enhance safety by reducing the likelihoodof the expandable member 3720 expanding enough to puncture or rupture avessel. The distal end of the lumen 3773 may be occluded, for example toinhibit debris from interfering with movement of the securing member3774. The cap 3775 may comprise a tool interface, for example ahexagonal recess, a protruding nut, etc. The tool interface can be usedduring assembly (e.g., to couple the securing member 3774 to theactuator 3780 and/or during a procedure.

The actuator 3780 may comprise a first lumen 3781 aligned with the firstlumen 3772 of the outer handle 3770. The first lumen 3781 may beconfigured to be coupled to a valve 3784 (e.g., a hemostasis valve 3784(e.g., a luer lock)), for example by comprising complementary threads,being configured to be tapped, being configured to receive a press-fit,etc. The actuator 3780 may comprise a valve in communication with thefirst lumen 3781 that is monolithic with the actuator 3780. A portion ofthe actuation tube assembly 3790 is fixably coupled to at least one ofthe first lumen 3781 and the valve 3784. A lumen of the actuation tubeassembly 3790 may be in fluid communication with a lumen of the valve3784.

The actuator 3780 may comprise a second lumen 3782 configured to fixablycouple the actuator 3780 to the securing member 3774. Depending on theshape and configuration of the securing member 3774, the second lumen3782 may be aligned with the second lumen 3773 of the outer handle 3770.The second lumen 3782 may comprise threads configured to receive andsecure an elongate threaded section of the securing member 3774. Thesecuring member 3774 may be monolithic with and extend from a distalsurface of the actuator 3780.

A locking member 3776 may optionally be positioned along the securingmember 3774 between the actuator 3780 and the outer handle 3770. Thelocking member 3776 may comprise, for example, a locking tuohy (e.g., asillustrated in FIG. 36K), a nut, a wingnut, etc. The locking member 3776comprises a threaded lumen configured to interact with the elongatethreaded section of the securing member 3774. The locking member 3776may comprise a textured outer surface configured to enhance grip of auser. The threads transmit rotational force on the locking member 3776into longitudinal movement along the securing member 3774. When thelocking member 3776 abuts a proximal end of the outer handle 3770, inwhat may be considered a locked position, the locking member 3776inhibits or prevents the actuator 3780 (and thus the actuation tubeassembly 3790 fixably coupled thereto) from moving distally. Locking theactuator 3780 can inhibit or prevent the splines 3722 of the expandablestructure 3720 from radially compressing and losing wall apposition.

The locking member 3776 may comprise any suitable structure forpreventing or inhibiting longitudinal motion of the securing member 3774relative to the outer handle 3770. In some embodiments, the lockingmember 3776 may be a non-threaded structure. For example, the lockingmember 3776 may comprise a clamp, which is secured to the securingmember 3774 via pressure and/or friction. The grip of the clamp lockingmember may be selectively loosenable and/or tightenable by the user. Insome embodiments, a clamp locking member 3776 may be biased in atightened position on the securing member 3774 by, for example, aspring. A clamp locking member 3776 may comprise a channel surroundingthe circumference of the securing member 3774, and the diameter of thechannel may be expanded or reduced by the turning of a screw that joinstwo ends of a clamp locking member 3776 to close the circumferencearound the securing member 3774. A clamp locking member 3776 maycomprise a biased projection configured to frictionally engage thesecuring member 3774, and can be temporarily released by the user. Aclamp locking member 3776 may be slideable or otherwise moveable alongthe securing member 3774 when in a loosened position and not slideableor otherwise moveable when in a tightened position. In some embodiments,a clamp locking member 3776 may be removable from the securing member3774 and selectively reattached at a desired position along the lengthof the securing member 3774. A clamp locking member 3776 may inhibit orprevent the distal displacement of the securing member 3774 relative tothe outer handle 3770 when a surface of the clamp locking member 3776abuts the proximal end of the outer handle 3770, placing the handle 3710in a locked position.

FIGS. 37Li-37Liii show an example method of operating a handle 3710 toradially expand an expandable member 3720. FIG. 37Li shows the handle3710 in a compressed state in which the actuator 3780 abuts or is closeto the locking member 3776, which abuts or is close to the outer handle3770. As shown to the left, the expandable member 3720 may be in aself-expanded state. The actuation tube assembly 3790 may proximallyretract upon radially outward self-expansion of the expandable structure3720.

As shown in FIG. 37Lii, as the actuator 3780 is proximally retracted,the securing member 3774, which is fixably coupled to the actuator 3780,slides proximally through the second lumen 3773 of the outer handle3770, the locking member 3776 stays in position on the securing member3774 and thus is proximally retracted, and the actuator tube assembly3790 slides proximally through the catheter shaft assembly 3706, thelumen 3764 of the handle base 3763, and the first lumen 3772 of theouter handle 3770. As the actuator tube assembly 3790 is proximallyretracted, the distal hub 3750 to which the actuator tube 3728 isfixably coupled is proximally retracted, imparting a longitudinallycompressive and radially expansive force on the splines 3722, which isexpanded radially further than the self-expanded state. As the splines3722 appose a vessel wall, the user can typically feel an oppositionforce in the actuator 3780, which is a benefit to a manual proceduresuch as illustrated in FIGS. 37Li-37Liii. Upon feeling the wallapposition, the user may adjust the expansion by further proximallyretracting the actuator 3780 and/or by distally advancing the actuator3780. Once the user is satisfied with the wall apposition provided bythe splines 3722 of the expandable member 3720, the user may engage thelocking member 3776.

As shown in FIG. 37Liii, the user rotates the locking member 3776. Thethreads of the threaded elongate section of the securing member 3774 andthe locking member 3776 translate the rotational force into longitudinalforce, and the locking member 3776 distally advances along the securingmember 3774 until the locking member 3776 abuts a proximal surface ofthe outer handle 3770. If a distal force is applied to the actuator3780, the actuator 3780 generally would not be able to distally movebecause the locking member 3776 is pressing against the proximal surfaceof the outer handle 3770.

FIGS. 37Li and 37Liv show another example method of operating a handle3610 to radially expand an expandable member 3720. Referring again toFIG. 37Li, the handle 3710 is in a compressed state.

As shown in FIG. 37Liv, as the locking member 3776 is rotated, thethreads of the threaded elongate section of the securing member 3774 andthe locking member 3776 translate the rotational force into longitudinalforce. The locking member 3776 bears against the proximal surface of theouter handle 3770, which forces the securing member 3774 to proximallyretract.

As the securing member 3774 is proximally retracted, the securing member3774 slides proximally through the second lumen 3773 of the outer handle3770, the actuator 3780, which is fixably coupled to the securing member3774, proximally retracts, and the actuator tube assembly 3790 slidesproximally through the catheter shaft assembly 3706, the lumen 3764 ofthe handle base 3763, and the first lumen 3772 of the outer handle 3770.As the actuator tube assembly 3790 slides is proximally retracted, thedistal hub 3750 to which the actuator tube 3728 is fixably coupled isproximally retracted, imparting a longitudinally compressive andradially expansive force on the splines 3722, which is expanded radiallyfurther than the self-expanded state. Throughout rotation of the lockingmember 3776, the locking member 3776 bears against the proximal surfaceof the outer handle 3770 such that, if a distal force is applied to theactuator 3780, the actuator 3780 generally would not be able to distallymove because the locking member 3776 is pressing against the proximalsurface of the outer handle 3770.

The force used to rotate the locking member 3776 may provide fine tuningas the locking member 3776 bears against the proximal surface of theouter handle 3770. Depending on the thread pitch, rotation of thelocking member by a certain rotational amount may proximally retract theactuation tube assembly 3790 a certain amount and/or radially expand theexpandable member 3720 a certain amount. For example, a 90° rotation ofthe locking member 3776 may radially expand the expandable member by adiameter of 1 mm in the absence of opposing forces. Finer and coarserpitches are also possible. A finer pitch allows finer tuning. A coarserpitch reduces the amount of rotation used to longitudinally move thecomponents, which can reduce procedure time. The locking member 3776 mayinclude indicia around its circumference to help the user identify theamount of rotation.

Combinations of the methods of FIGS. 37Li-37Liv are also possible. Forexample, the user may first manually retract the actuator 3780, forexample to feel the wall apposition, rotate the locking member 3776 toabut a proximal end of the outer handle 3770, and then fine tune theamount of expansion by rotating the locking member 3776. For example, ifthe user desires to expand the expandable member 3720 by a diameter of 2mm beyond wall apposition (e.g., the diameter of the vessel measure atsystolic maximum), which can provide secure anchoring, the user canrotate the locking member 3776 by 180° after abutting the outer handle3770.

FIG. 37M is a side cross-sectional view of example components of ahandle base 3763. To provide example context, FIG. 37M also includesportions of the actuation shaft assembly 3790, part of the cathetershaft assembly 3706, and connector tubing 3798. The handle base 3763comprises a lumen 3764 configured to receive a sealing element 3766, theactuation tube assembly 3790, and/or the catheter shaft assembly 3706.When the handle base 3763 is inserted into the recess of the outerhandle 3770, the lumen 3764 is aligned with the first lumen 3772 of theouter handle 3770.

The catheter shaft assembly 3706 may be fixably coupled to the handlebase 3763 by inserting the proximal end of the catheter shaft assembly3706 into the lumen 3764 and then securing the catheter shaft assembly3706 to the handle base 3763, for example by adhesive (e.g.,cyanoacrylate), welding, soldering, combinations thereof, etc. Thehandle base 3763 may comprise a shoulder 3768 extending into the lumen3764 configured to interact with the proximal end of the catheter shaftassembly 3706. For example, the shoulder 3768 may provide a stop forinsertion of the catheter shaft assembly 3706 into the lumen 3764, whichcan facilitate manufacturing. The actuation tube assembly 3790 maycomprise a plurality of components, for example including multiple typesof tubing. Fewer components generally may reduce manufacturingcomplexity of the actuation tube assembly 3790. Multiple components canprovide specialization of different portions of the actuation tubeassembly 3790. If coupling components together is easier than modifyingfewer components for particular functions, multiple components canreduce manufacturing complexity of the actuation tube assembly 3790. Theactuation tube assembly 3790 illustrated in FIG. 37M comprises a firsthypotube 3791, a second hypotube 3792, and the actuation tube 3728. Theactuation tube assembly 3790 may comprise an actuation tube assemblylumen 3793 extending from the proximal end of the actuation tubeassembly 3790 to the distal end of the actuation tube assembly 3790. Theactuation tube assembly lumen 3793 may comprise segments in eachcomponent (e.g., the first hypotube 3791, second hypotube 3792, andactuation tube 3728) of the actuation tube assembly 3790, which may bealigned along a longitudinal axis of the actuation tube assembly 3790.The lumens of the components may be joined and/or aligned by, forexample, positioning a component of a smaller outer diameter within thelumen of a component with a larger diameter inner diameter. The innersurfaces of the actuation tube 3728 and/or any of the other componentscomprising the actuation tube assembly lumen 3793 may comprise a lining(e.g., fluoropolymer (e.g., PTFE, PVDF, FEP, Viton, etc.)) to reducefriction with a guidewire inserted through the lumen 3793. The outersurfaces of the actuation tube 3728 and/or any of the other componentscomprising the actuation tube assembly 3790 may comprise a lining (e.g.,fluoropolymer (e.g., PTFE, PVDF, FEP, Viton, etc.)) to reduce frictionbetween the actuation tube assembly 3790 and the catheter shaft assembly3706 or the lumen 3674 of the handle base 3763.

Referring again to FIG. 37L, a proximal end of the actuation tubeassembly 3790, more specifically the proximal end of the first hypotube3791, is fixably coupled to at least one of the actuator 3780 and thevalve 3784. The first hypotube 3791 extends from the actuator 3780 intothe proximal portion of lumen 3764 of the handle base 3763, through thesealing element 3766. The sealing element 3766 provides a fluid-tightseal between the actuation tube assembly 3790 and the handle base 3763.The first hypotube 3791 may be machined to include a first portion 3791Aand a second portion 3791B having a smaller diameter than the firstportion 3791A. The first hypotube 3791 may include one or a plurality ofapertures 3794, which can provide fluid communication between theactuation tube assembly lumen 3793 and the lumen 3764. As described infurther detail herein, fluid (e.g., saline, heparinized saline,contrast, etc.) injected into the lumen 3793 through the valve 3784 canflow through the lumen 3793 until the apertures 3794, and then maycontinue to flow through the lumen 3793 or out of the apertures 3794 andthen through the lumen 3764. In some embodiments, the first hypotube3791 may be devoid of apertures 3794 and configured such that fluidinjected into the lumen 3793 flows only through the lumen 3793.

The first portion 3791A of the first hypotube 3791 may have an outerdiameter that is slightly smaller than the inner diameter of the lumen3764. Such a diameter difference can reduce (e.g., minimize) the spacebetween the outer surface of the first portion 3791A and the innersurface of the handle base 3763 to reduce (e.g., minimize) fluid flowingout of the apertures 3794 from flowing proximally and/or can reducefriction between the first portion 3791A and the inner surface of thehandle base 3763. The second portion 3791B of the first hypotube 3791may provide an arcuate or toroidal gap or lumen between an outer surfaceof the second portion 3791B of the first hypotube 3791 and the innersurface of the handle base 3763. Such a diameter difference can promotefluid flowing out of the apertures 3794 to flow distally through thelumen 3764. The first hypotube 3791 may comprise a biocompatiblematerial such as, for example, stainless steel, nitinol, plastic, etc.Although described as a hypotube, the first hypotube 3791 may bemachined from a flat sheet, a solid rod, etc.

A proximal end of the lumen 3764 of the handle base 3763 may include anexpanded diameter portion configured to receive a sealing element 3766(e.g., comprising an o-ring, a shim, a gasket, etc.). The sealingelement 3766 may be positioned between the first hypotube 3791 and thehandle base 3763. The sealing element 3766 can seal a proximal end ofthe lumen 3764 to inhibit or prevent fluid flowing though the apertures3794 from flowing out the handle base 3763.

A second hypotube 3792 may comprise an outer diameter that is slightlysmaller than the inner diameter of the first hypotube 3791 such that aproximal end of the second hypotube may be inserted into a distal end ofthe first hypotube 3791. The second hypotube 3792 may be fixably coupledto the first hypotube 3791, for example by adhesive (e.g.,cyanoacrylate), welding, soldering, combinations thereof, etc. Thesecond hypotube 3792 may extend into a proximal end of the cathetershaft assembly 3706. The outer diameter of the second hypotube 3792 isless than the inner diameter of the lumen 3764, forming an arcuate ortoroidal gap or lumen, which can provide an open segment for fluid toflow and conductors to extend. The second hypotube 3792 may comprise abiocompatible material such as, for example, stainless steel, nitinol,plastic, etc. Although described as a hypotube, the second hypotube 3792may be machined from a flat sheet, a solid rod, etc.

The actuation tube 3728 extends from the proximal portion 3704 of thecatheter system 3700 to the distal portion 3704 of catheter system 3700.The actuation tube 3728 may be fixably coupled to the second hypotube3792, for example by adhesive (e.g., cyanoacrylate), welding, soldering,combinations thereof, etc. The second hypotube 3792 may comprise a lumenhaving an inner diameter that is slightly larger than the outer diameterof the actuation tube 3728 such that a proximal end of the actuationtube 3728 may extend into a distal end of the second hypotube 3792. Thesecond hypotube 3792 may comprise a lumen having an inner diameter thatis slightly larger than the outer diameter of the actuation tube 3728,and a distal end of the second hypotube 3793 may extend into a proximalend of the actuation tube 3728. The actuation tube 3728 may comprise aplurality of layers. For example, the actuation tube 3728 may comprise aflexible polymer (e.g., polyimide, polyamide, PVA, PEEK, Pebax,polyolefin, PET, silicone, etc.), a reinforcing layer (e.g., comprisinga braid, a coil, etc.), and an inner liner (e.g., fluoropolymer (e.g.,PTFE, PVDF, FEP, Viton, etc.)).

The second hypotube 3792 optionally may be omitted, for example byextending the first hypotube 3791 distally and/or extending the flexiblepolymer of the actuation tube 3728 proximally. The second hypotube 3792may comprise a biocompatible material such as, for example, stainlesssteel, nitinol, plastic, etc.

The actuation tube assembly 3790 and the catheter shaft assembly 3706combine to form two concentric lumens between the handle 3710 and theexpandable structure 3720. The actuation tube assembly lumen 3793 of theactuation tube 3728 forms the inner lumen. The inner lumen 3793 may bein fluid communication with the hemostasis valve 3784. The distalterminus of the inner lumen 3793 is the distal end of the actuator tubeassembly 3790, which is coupled to the proximal hub 3740. The hemostasisvalve 3784 may allow insertion of a guidewire, which can extend throughthe actuation tube 3728 and distally beyond the distal hub 3750 of theexpandable structure 3720. The outer lumen 3707 is arcuate or toroidalbetween the outer surface of the actuation tube assembly 3790 and theinner surface of the catheter shaft assembly 3706. The distal terminusof the outer lumen 3707 is the distal end of the catheter shaft assembly3706, which is coupled to the proximal hub 3740.

The hemostasis valve 3784 may be used to inject fluids (e.g., saline,heparinized saline, contrast, etc.). Fluid may be injected into thehemostatsis valve 3784 (e.g., via IV bag, syringe, etc.). The fluid canflow through the first hypotube 3791 until the apertures 3794. The fluidmay continue to flow through the inner lumen 3793 of the actuation tubeassembly 3790 out of the distal hub 3750 and/or may flow through theapertures 3794 and then through the outer lumen 3707 out of the proximalhub 3740. Referring again to FIG. 37G-37I, the proximal hub 3740comprises peripheral lumens 3743. Fluid flows out of the outer lumen3707 through at least one of the peripheral lumens 3743. Fluid flowthrough a peripheral lumen 3743 may be inversely proportional to a levelof occlusion of that peripheral lumen 3743 (e.g., due to occupation byconductors 3712). In some embodiments, the first hypotube 3791 may notcomprise apertures 3794, and fluid may flow only through the inner lumen3793 of the actuation tube assembly 37990 to the distal hub 3750.

Flushing fluid may provide a slight positive pressure within the lumens,which can inhibit blood from flowing into the catheter system 3700.Flushing fluid may wash the expandable structure 3720 and/or otherportions of the catheter system 3700, which can inhibit thrombusformation during the medical procedure. If the fluid comprises contrast,flushing fluid can direct contrast to aid fluoroscopy and visualizationof the expandable structure 3720 relative to the vessel.

The handle base 3763 may comprise an aperture 3765 extending through asidewall into the lumen 3764, for example in communication with thearcuate or toroidal gap or lumen between the second hypotube 3792 andthe handle base 3763. The conductors 3712 may extend from the electricalconnector 3799, through the connector tubing 3798, through the aperture3765, into the outer lumen 3707, through the proximal hub 3740 (e.g., asshown in FIG. 37I), and to the electrodes 3724.

FIG. 37N is a perspective view of a proximal end of an example of acatheter shaft assembly 3706 and second hypotube 3792. The cathetershaft assembly 3706 surrounds the actuation tube 3728 from the handle3710 to the proximal hub 3740. The actuation tube 3828 may be proximallyretracted and/or distally advanced relative to catheter shaft assembly3706.

The catheter shaft assembly 3706 may comprise a plurality of layers. Forexample, the catheter shaft assembly 3706 may comprise a flexiblepolymer (e.g., polyimide, polyamide, PVA, PEEK, Pebax, polyolefin, PET,silicone, etc.), a reinforcing layer (e.g., comprising a braid, a coil,etc.), and an inner liner (e.g., fluoropolymer (e.g., PTFE, PVDF, FEP,Viton, etc.)). Different layers may be present along differentlongitudinal segments.

The flexible polymer may comprise, for example, polyimide, polyamide,PVA, PEEK, Pebax, polyolefin, PET, silicone, etc.). Differentlongitudinal sections of the tubing may have different durometers alongthe length of the catheter shaft assembly 3706. For example, thecatheter shaft assembly 3706 may transition from a higher durometer,indicating a harder material, to a lower durometer, indicating a softermaterial, from proximal to distal. The lengths and durometers of thevariable durometer sections may be matched to suit the differentanatomical structures in which those sections will reside during aprocedure. For example, the catheter shaft assembly 3706 may comprise atleast five different durometer sections: a first section having adurometer of about 72 D having a length configured to extend from thehandle 3710 into the body through a carotid vein proximal to the heart;a second section having a durometer of about 63 D and a third sectionhaving a durometer of about 55 D together having a length configured topass through the right atrium and right ventricle; and a fourth sectionof having a durometer about 40 D and a fifth section having a durometerof about 25 D together having a length configured to extend through thepulmonary valve and into the right pulmonary artery. The flexibility ofthe fourth section and/or the fifth section may allow the catheter shaftassembly 3706 to bend and fixate the catheter shaft assembly, forexample against a left side of the pulmonary trunk, which can aid inproperly positioning the expandable member 3720 in a pulmonary artery.At least one of the fourth section and the fifth section may comprise ahinge 3726, for example as described herein, which can resist kinking ifthe catheter shaft assembly 3706 makes a sharp (e.g., 90°) turn, forexample from the pulmonary trunk to the right pulmonary artery. Thelengths of the five sections may be, in terms of percentage of the totallength of the catheter shaft assembly 3706, between about 50-90% for thefirst section and between about 1 to 20% for each the remainingsections. For example, the lengths may be about 73%, 7.5%, 5.5%, 5.5%,and 8.5%, respectively. The first section may be longer or shorterdepending on the total length of the catheter shaft assembly 3706, whichmay depend on the pathway to the pulmonary artery, the amount residingoutside the body, etc.

The catheter shaft assembly 3706 may have a length between about 50 and200 cm (e.g., about 50 cm, about 75 cm, about 100 cm, about 125 cm,about 150 cm, about 200 cm, ranges between such values, etc.). Thelength of the catheter shaft assembly 3706 may be suitable to positionthe expandable structure 3720 in a pulmonary artery from a peripheralvein such as a jugular vein, a femoral vein, a radial vein, or othersuitable access location.

The flexibility of the catheter shaft assembly 3706 can be additionallyor alternatively modulated by other means, such as reinforcing andadjusting various sections of the catheter shaft assembly 3706. Forexample, if the catheter shaft assembly 3706 comprises a reinforcingcoil, a pitch of the coil may be varied. For another example, if thecatheter shaft assembly 3706 comprises a reinforcing braid, a parameter(e.g., number, thickness, braid angle, etc.) of the braid wires in maybe varied. For yet another example, the thickness may vary. For stillanother example, the composition may vary (e.g., different sectionscomprising at least one different material). Combinations of two or allvariations is also possible. Rather than being discrete sections, theflexibility may transition from one section to the next section.

FIG. 37N shows the proximal end of catheter shaft assembly 3706comprising a first segment 3708 and a second segment 3709 thicker thanthe first segment 3708. The change in thickness at the proximal end ofthe actuation shaft assembly 3706, for example the first segment 3708,may provide a mechanism of strain relief. The second segment 3709 mayhave an outer diameter configured to fit in the lumen 3764 of the handlebase 3763 to be fixably coupled to the handle base 3763.

FIG. 37O is a side cross-sectional view of an example connection betweena distal end of a catheter shaft assembly 3706 and a proximal hub 3740of an expandable structure 3720. The distal end of the catheter shaftassembly 3706 may comprise a hinge 3726 configured to be fixably coupledto the proximal hub 3740.

The hinge 3726 may comprise, for example, a coil or series ofinterspaced coils that extend slightly beyond the distal end of otherparts of the catheter shaft assembly 3760 such as the PTFE liner, wirebraid, and flexible tubing. The coil hinge 3726 may comprise one or aplurality of wires (e.g., one wire, two wires, three wires, or more)configured in a helical pattern. The wires comprise helically woundcoils having a uniform pitch. Each coil may occupy the space between thehelical revolutions of the other coils. FIG. 37P is a perspective viewof an end of an example of a hinge 3726 comprising three wires. Thehinge 3726 may comprise a hypotube, for example cut to include a coilpattern and/or opposing circumferential slots.

The hinge 3726 may be positioned around the outer surface of theproximal section 3741 of the proximal hub 3740. The hinge 3726 may befixably coupled to the proximal hub 3740 by adhesive (e.g.,cyanoacrylate), welding, soldering, combinations thereof, etc. Thedistal end of the catheter shaft assembly 3706 may comprise layers thatare proximally spaced from the distal end of the hinge 3726 by about0.01 inches to about 0.1 inches (e.g., about 0.01 inches, 0.025 inches,0.05 inches, 0.075 inches, 0.01 inches, ranges between such values,etc.), which can provide sufficient space for the hinge 3726 to beaffixed (e.g., directly affixed) to the proximal hub 3740 withoutinterference from those layers. The distal end of the flexible tubing,wire braid, liner, and/or other layers of the catheter shaft assembly3706 may be longitudinally spaced from the proximal end of the proximalhub 3740, which can reduce transmission of forces on the catheter shaftassembly 3706, for example absorbed by the hinge 3726, from beingtransmitted to the expandable structure 3720.

The hinge 3726 may be covered by a hinge tube 3711, which may compriseurethane or another suitable material, and which extends from the distalend of the hinge 3726 past the proximal end of the hinge 3726, forexample to inhibit pinching of tissue by the hinge 3726. The hinge tube3711 may be heat cured to the hinge 3726 and outer circumference ofother components of the catheter shaft assembly 3706. The hinge tube3711 may be aligned substantially flush with or overlap the distalportion 3742 of the proximal hub 3740. The hinge tube 3711 may form afluid seal with the proximal hub 3742, for example so that fluid flowingin the lumen 3707 exits the peripheral lumens 3744.

FIG. 37Q is a perspective view of an example handle 3701 of a cathetersystem (e.g., the catheter system 3700) in an unlocked configuration.FIG. 37R schematically illustrates a perspective cross-sectional view ofthe handle 3701 of FIG. 37Q along the line 37R-37R. In addition to thehandle 3701, FIGS. 37Q and 37R show a portion of a catheter shaftassembly 3706 extending therefrom. The handle 3701 is configured toremain outside the body. The handle 3701 comprises an outer handle 3713which the user may grasp. The outer handle 3713 comprises a lumen 3714extending from the proximal end of the outer handle 3713 to the distalend of the handle outer 3713. The lumen 3714 may be configured toreceive a tubular base 3715, which may be partially inserted into thelumen 3714 and fixably coupled to the outer handle 3713. The tubularbase 3715 may be generally cylindrical in shape and may comprise atapered distal end. Other geometries (e.g., polygonal) are alsopossible. The tubular base 3715 may extend out of the distal end of thelumen 3714 (as shown in FIGS. 37Q and 37R) or may be entirely receivedwithin the lumen 3714. The tubular base 3715 comprises a channel 3716extending from the proximal end of the tubular base 3715 to the distalend of the tubular base 3715. The tubular base 3715 may comprise ashoulder 3717 extending into the channel 3716 configured to interactwith the proximal end of the catheter shaft assembly 3706. The cathetershaft assembly 3706 may be fixably coupled to the tubular base 3715 byinserting the proximal end of the catheter shaft assembly 3706 into thechannel 3716 and then securing the catheter shaft assembly 3706 to thetubular base 3715, for example by adhesive (e.g., cyanoacrylate),welding, soldering, combinations thereof, etc. The actuation tubeassembly 3790 can be slidably received in the channel 3716 and portionsof the actuation tube assembly 3790 can extend through the cathetershaft assembly 3706, for example as described herein. The tubular base3715 may comprise an annular recess 3718 in the sidewall of the channel3716 positioned near the proximal end of the channel 3716 configured toreceive a sealing element (e.g., comprising an o-ring, a shim, a gasket,etc.) The sealing element may be positioned between the first hypotube3791 and the tubular base 3715, and may inhibit or prevent fluid flowingthrough the apertures 3794 of the first hypotube 3791 from flowing outthe tubular base 3715. In some embodiments, the annular recess 3718 mayextend to the proximal end of the tubular base 3715.

The proximal end of the actuation shaft assembly 3790 can be coupled toan actuation pin 3730. The actuation pin 3730 comprises an actuationchannel 3731 extending from the proximal end of the actuation pin 3730to the distal end of the actuation pin 3730. The actuation channel 3731is configured to receive the proximal end of the actuation tube assembly3790 (e.g., the first hypotube 3791), which can be partially insertedinto the actuation channel 3731 and fixably coupled to the actuationchannel 3731, for example by adhesive (e.g., cyanoacrylate), welding,soldering, combinations thereof, etc. The actuation pin 3730 maycomprise an expanded diameter grip 3732 for facilitating the grip of theuser. The expanded diameter grip 3732 may comprise a textured surface.The actuation channel 3731 may comprise an expanded diameter portion atits proximal end configured to receive a tubing connector 3797. Thetubing connector 3797 may be Y-shaped, including two intersectingchannels. The channels of the tubing connector 3797 may be used for theinsertion of a guidewire, electrical conductors, and/or the injection offluids into the actuation tube assembly lumen 3793, as describedelsewhere herein. The connector tubing 3797 may comprise a luer fittingincluding a single lumen.

The outer handle 3713 may comprise a void 3719 extending between anupper surface and a lower surface and intersecting the lumen 3714 of theouter handle 3713. In some embodiments, the void 3719 may extend to aside surface of the handle 3713 such that it opens to an upper surface,lower surface, and side surface of the outer handle 3713. The void 3719may be configured to receive a locking member 3777. FIG. 37S is aperspective view of an example of the locking member 3777. The lockingmember 3777 may comprise a generally cylindrical body and a channel 3778extending from a proximal side of the locking member 3777 to a distalside of the locking member 3777 through the generally cylindrical body.The locking member 3777 may comprise at least one projection 3789extending radially inwardly from the sidewall of the channel 3778. Ifthe locking member comprises two projections 3789, the two projections3789 may be on opposite sides of the channel 3778. If the channel 3778is oblong, the projection 3778 may be positioned along thelonger-dimensioned length of the channel 3778 (e.g., at a centralposition along the longer-dimensioned length). The locking member 3777may comprise a tab 3779 extending away from the channel 3778, forexample in a direction perpendicular to the longitudinal axis of thechannel 3778. The tab 3779 and generally cylindrical body may form ab-shape, d-shape, p-shape, or q-shape. The actuation pin 3730 may extendthrough the channel 3778. The handle 3701 may comprise a bushing 3796configured to be received in the proximal end of the outer handle 3713where the bushing 3796 may be affixed. The bushing 3796 may comprise achannel through which the actuation pin 3730 extends. The locking member3777 may be rotatable about the longitudinal axis of the actuation pin3730. The locking member 3777 can be configured to place the handle 3701and the actuation tube assembly 3790 in a locked or unlockedconfiguration. In some embodiments, the degree of rotation of thelocking member 3777 may be limited. As seen in the example of FIG. 37Q,the tab 3779 may only allow the locking member 3777 to rotateapproximately a quarter-turn before the tab 3779 abuts a portion of theouter housing 3713.

FIG. 37T schematically illustrates an expanded perspectivecross-sectional view of the handle 3701 of FIG. 37Q in an unlockedconfiguration in the area of the circle 37T of FIG. 37R. The actuationpin 3730 may comprise a series of ridges 3733 and intervening notchesspaced along its outer circumference. The ridges 3733 may beperpendicular to the longitudinal axis of the actuation pin 3730. Theridges 3733 may extend away from the circumference of the actuation pin3730 along two opposing sides of the actuation pin 3730. For example,the circumference of the actuation pin 3730 may be proportioned intoapproximate quarters, and the ridges 3733 may extend from twonon-adjacent quarters of the circumference. The quarters of thecircumference where the ridges 3733 do not extend may comprise flatsurfaces extending along the length of the actuation pin 3730, as shownin FIG. 37Q (one of the flat surfaces is visible). The projection 3789along the channel 3778 of the locking member 3777 may be configured tobe received in a notch between two of the ridges 3733. The projection3789 may be configured to mate with the outer circumference of theactuation pin 3730 when positioned in a notch. When in an unlockedconfiguration, the rotational orientation of the locking member 3777positions the projection 3789 adjacent to a flattened surface of theactuation pin 3730. As shown in FIG. 37T, the projection 3789 is notpositioned between the ridges 3733 in an unlocked configuration. The tab3779 may be positioned in a first position (e.g., an upward position,extending away from the surface of the outer handle 3713), when in anunlocked configuration. In the unlocked configuration, the actuation pin3730 may be translated in a proximal or distal direction by the user,which causes the translation of the actuation tube assembly 3790, whichis rigidly affixed to the actuation pin 3730. The user may expand theexpandable structure 3720 by pulling the actuation pin 3730 in aproximal direction. The user may compress the expandable structure 3720by pushing the actuation pin 3730 in a distal direction. The expandablestructure 3720 may assume a self-expanded state when in an unlockedconfiguration without a user pushing or pulling on the actuation pin3730. The locking member 3777 may be devoid of a tab 3777, for examplecomprising a textured surface like a thumb wheel.

FIG. 37U is a perspective view of the handle 3701 of FIG. 37Q in alocked configuration. The user may place the handle 3701 in a lockedconfiguration by moving the tab 3779 of the locking member 3777 to asecond position to rotate the locking member 3777 approximately aquarter-turn around the actuation pin 3730. The outer handle 3713 maycomprise a shoulder 3795 (FIG. 37Q) to limit the rotation of the tab3779. In the locked configuration, the tab 3779 may no longer extendaway from the surface of the handle 3701, but may be relatively flushwith the surface of the handle 3701. The different positioning of thetab 3779 in unlocked and locked configurations, as seen in FIGS. 37Q and37U, may provide a visually discernable indicator of the configurationthe handle 3701.

FIG. 37V schematically illustrates a perspective cross-sectional view ofthe handle 3701 of FIG. 37U along the line 37V-37V. When in a lockedconfiguration, the projections 3789 (two projections 3789 in theillustrated embodiment) have been rotated into two of the notchesbetween the ridges 3733 of the actuation pin 3730, inhibiting orpreventing the actuation pin 3730 and the actuation tube assembly 3730coupled thereto from moving in a proximal direction and from moving in adistal direction. The locking of the handle 3730 can inhibit or preventthe expandable structure 3720 from further radially expanding and fromradially compressing. The user may partially turn the tab 3779 at anapproximate desired locking position and may then push or pull on theactuation pin 3779 until the projection 3789 falls into place betweenthe ridges 3733. In some embodiments, the width of the projections 3789may form a tight interference fit with the notches such that a “snap” isfelt when locking or unlocking the locking member 3777. To unlock thelocking member 3777, the user may place the tab 3779 back into anupright position, rotating approximately a quarter-turn in the oppositedirection used to lock the locking member 3777. The locking member 3777may be configured to be turned more or less than a quarter turn toswitch between locked and unlocked configurations.

The handle 3701 can allow the user to quickly and/or easily adjust theexpansion of the expandable structure 3720 by pushing or pulling theactuation pin 3730 a desired amount. The actuation pin 3730 andactuation tube assembly 3790 can be locked in position along thelongitudinal axis according to discrete increments determined by thepitch of the series of ridges 3733 and intervening notches. The pitchand the projection 3789 can be modified to allow either narrower orbroader tuning of the expansion and compression of the expandablestructure 3720 (e.g., the widths can be smaller than shown in FIGS.37Q-37U to provide more locking positions). In some embodiments, thelocking member 3777 may comprise only one projection 3789 and/or theactuation pin 3730 may comprise only one flattened surface. In someembodiments, the actuation pin 3730 may comprise a textured surface(e.g., comprising grooves, bumps, flanges, etc.) configured tofrictionally engage the locking member 3777. The projection 3789 andnotches between ridges 3733 could be corresponding saw-tooth shapes. Insuch embodiments, the locking member 3777 may be configured to allowtranslation of the actuation pin 3730 (e.g., back to the self-expandedstate of the expandable member 3720 in a failure event) in a lockedconfiguration if enough force is applied to force the ridges 3733 overthe saw tooth projection 3789.

FIG. 38A is a perspective view of an example of a catheter system 3800.The system 3800 may comprise a proximal portion configured to remain outof the body of a subject and a distal portion configured to be insertedinto vasculature of a subject, for example as described with respect tothe catheter system 3800. The system 3800 comprises an expandablestructure 3820. The expandable portion 3820 is coupled to a cathetershaft 3806. In some embodiments, the system 3800 comprises a strainrelief 3826 between the catheter shaft 3806 and the expandable structure3820. The strain relief 3826 may be at least partially in a lumen of thecatheter shaft 3806.

The expandable structure 3820 includes a plurality of splines 3822. Thesplines 3822 comprise a sinusoidal or wave or undulating or zig-sagshape. The sinusoidal shape may provide more flexibility in electrodepositioning. For example, electrodes may be placed at peaks, troughs,and/or rising or falling portions. In some embodiments, electrodes arepositioned proud of peaks, which can allow the electrodes to make closecontact with vessel walls. The sinusoidal shape may provide better wallapposition, for example creating anchor points at peaks. At least one ofthe splines 3822 comprises an electrode array comprising a plurality ofelectrodes to form an electrode matrix. The number of electrodes in theelectrode matrix, electrode sizing, electrode spacing, etc. may be inaccordance with other systems described herein. In some embodiments, thesplines 3822 comprise wires having a diameter between about 0.006 inches(approx. 0.15 mm) and about 0.015 inches (approx. 0.38 mm) (e.g., about0.006 inches (approx. 0.15 mm), about 0.008 inches (approx. 0.2 mm),about 0.01 inches (approx. 0.25 mm), about 0.012 inches (approx. 0.3mm), about 0.015 inches (approx. 0.38 mm), ranges between such values,etc.). In some embodiments, the splines 3822 may be cut from a hypotubeand then shape set into the sinusoidal shape.

FIG. 38B is a perspective view of a portion of the catheter system 3800of FIG. 38A in a collapsed state. The illustrated portion includes partof the catheter shaft 3806, the strain relief 3826, and the expandablestructure 3820. The illustrated portion also includes an actuationmember 3828, which can be coupled to an actuator mechanism to causeexpansion or retraction of the expandable structure 3820. The actuationmember 3828 may be in a lumen of the catheter shaft 3806. A guidewire3815 is also shown in the lumen of the actuation member 3828. In someembodiments, the actuation member 3828 comprises a lumen capable ofreceiving a 0.018 inch guidewire 3815. The actuation member 3828 maycomprise a tubular structure, for example as described with respect tothe actuation tube assembly 3790. The actuation member 3828 may comprisea wire with or without a lumen.

FIG. 38C is a side view of a portion of the catheter system 3800 of FIG.38A in an expanded state. Operation of the actuation mechanism 3612 cancause the expandable structure 3620 to expand and contract. For example,rotation and/or longitudinal movement of the actuation mechanism 3612can cause the actuator wire 3628 to proximally retract, the cathetershaft 3606 to distally advance, or a combination thereof, each of whichcan push the splines 3622 radially outward. In some embodiments, thedistal ends of the splines 3622 are coupled to a distal hub that iscoupled to the actuator wire 3628, and the proximal ends of the splines3622 are coupled to a proximal hub that is coupled to the catheter shaft3606. In the expanded state, the expandable structure 3620 comprisessplines 3622 that are spaced from each other generally parallel to alongitudinal axis at a radially outward position of the splines 3622.The parallel orientation of the splines 3622 can provide circumferentialspacing of the splines 3622, for example in contrast to singular splinesor wires that may circumferentially bunch. In some embodiments, thesplines 3622 comprise wires having a diameter between about 0.006 inches(approx. 0.15 mm) and about 0.015 inches (approx. 0.38 mm) (e.g., about0.006 inches (approx. 0.15 mm), about 0.008 inches (approx. 0.2 mm),about 0.01 inches (approx. 0.25 mm), about 0.012 inches (approx. 0.3mm), about 0.015 inches (approx. 0.38 mm), ranges between such values,etc.).

In some embodiments, the diameter of the expandable structure 3820 inthe expanded state is between about 15 mm and about 30 mm (e.g., about15 mm, about 20 mm, about 22 mm, about 24 mm, about 26 mm, about 28 mm,about 30 mm, ranges between such values, etc.). In some embodiments, thesplines 3822 may be self-expanding such that an actuation mechanismallows the splines to self-expand from a compressed state for navigationto a target site to an expanded state for treatment at the target site.In certain such embodiments, the diameter of the expandable structure3820 in the expanded state may be oversized to most the intendedvasculature of most subjects to ensure vessel wall apposition. In someembodiments, the splines 3822 may be non-self-expanding such that thesplines only expand upon operation of an actuation mechanism. In someembodiments, the splines 3822 may be self-expanding, and an actuationmechanism may further expand the splines 3822, which may provide anadjustable expandable structure 3820 diameter usable for a range ofvessel sizes, wall apposition forces, etc. Embodiments in which theexpandable structure 3820 does not appose the wall in the event of anerror could be advantageous for safety, for example as described withrespect to the system 2200.

FIG. 38D is a partial side cross-sectional view of the expandablestructure 3820. The expandable structure comprises a distal hub 3830comprising a plurality of channels 3832 in which the distal segments ofthe splines 3822 are positioned. In some embodiments, the distalsegments of the splines 3822 are not fixed such that they can slide inthe channels 3832, which can allow each spline 3822 to moveindependently, which may accommodate curvature at a deployment site. Incertain such embodiments, the distal ends of the splines 3822 comprise astop member (e.g., an expanded diameter ball weld) that inhibits orprevents the distal segments from exiting the channels 3832 and thedistal hub 3830. Such a system may also be used with other cathetersystems and expandable structures described herein (e.g., the expandablestructures 3620, 3630, 3640, 3650).

FIG. 38E is a partial side cross-sectional view of an expandablestructure 3840. The expandable structure 3840 comprises a plurality ofsplines 3842 having a sinusoidal shape. The expandable structure 3840comprises a plurality of electrodes 3844 at peaks of a plurality ofthree of the splines 3842 to form a 3×4 electrode matrix. In someembodiments in which three splines comprise electrodes, a middle orcentral spline may be different than the circumferentially adjacentsplines. For example, the middle spline may comprise more or fewerpeaks, peaks that are longitudinally offset, etc. Upon expansion of theexpandable structure 3820, the electrodes of the electrode matrix may beselectively activated for testing nerve capture, calibration, and/ortherapy, for example as described herein.

FIG. 39A is a side view of an example of an expandable structure 3900.The expandable structure 3900 may be incorporated into a catheter systemsuch as the catheter systems described herein. The expandable structure3900 comprises a plurality of splines 3902. The splines 3902 are bent toform parallel portions 3904 that are radially offset. The parallelportions 3904 may comprise electrodes, electrode structures, etc. Insome embodiments, bent portions of the splines act as hinges to urge theoffset parallel portions 3904 against vessel walls. The expandablestructure 3900 may be self-expanding, expandable using an actuationmechanism, and combinations thereof, for example as described herein.FIG. 39A illustrates four splines 3902 that are circumferentially offsetby about 90°, but other numbers of splines and offset are also possible.

FIG. 39B is an end view of an example of another expandable structure3910. The expandable structure 3910 comprises six splines 3912, three ofwhich are grouped on one side of a plane 3914 and three of which aregrouped on the other side of the plane 3914. In some embodiments, onegroup of splines 3912 may comprise electrodes and the other group ofsplines 3912 may be free of electrodes and used for wall apposition,anchoring, etc. In some embodiments, FIG. 39B is representative of aportion of FIG. 36H. For example, the expandable structures 3900, 3910may comprise a portion (e.g., half) of the splines described withrespect to FIGS. 36A-36O.

FIG. 39C is an end view of an example of yet another expandablestructure 3920. The expandable structure 3920 comprises six splines 3922and six splines 3924. Like the splines 3902, the splines 3922 compriseradially offset parallel portions. The splines 3924 are each generallyparallel to an adjacent spline up to the bend, and continue to extendradially outward.

FIG. 39D is an end view of an example of still another expandablestructure 3930. The expandable structure 3930 comprises a first spline3932, a second spline 3934, and six splines 3936. Like the splines 3902,the spline 3922 comprises a radially offset parallel portion. Like thesplines 3902, the spline 3924 also comprises a radially offset parallelportion that is radially offset in a different direction than the spline3922. The splines 3936 are extend radially outward, with one spline 3936circumferentially between the splines 3932, 3934. The splines 3932,3934, and the spline 3936 circumferentially between the splines 3932,3934 may comprise electrodes forming an electrode matrix. In someembodiments, FIG. 39D is representative of a portion of FIG. 36L. Forexample, the expandable structures 3900, 3910, 3920, 3930 may comprise aportion (e.g., half) of the splines described with respect to FIGS.36A-36O.

The parallel portions of the expandable structures 3900, 3910, 3920,3930 may be straight, recessed, crowned, sinusoidal, longitudinallyoffset, carrying a mesh, etc., for example as described herein.

FIG. 40A is a perspective view of an example of a strain relief 4026 fora catheter system. The strain relief 4026 can act like a flexible hingeto decouple catheter forces from an expandable structure, for example inthe catheter systems described herein. The strain relief 4026 comprisesa spring. The spring may comprise a variable helix, which can varyflexibility longitudinally. In some embodiments, the spring may beembedded in a polymer. In some embodiments, the polymer may have adurometer that varies longitudinally in longitudinal alignment withand/or longitudinally offset from helix variability. In someembodiments, a strain relief does not comprise a spring, but comprises apolymer having longitudinally varying durometer. In some embodiments, aplurality of helices of opposite sense may be braided to form a strainrelief.

FIG. 40B is a perspective view of another example of a strain relief4027 for a catheter system. The strain relief 4027 can act like aflexible hinge to decouple catheter forces from an expandable structure,for example in the catheter systems described herein. The strain relief4027 comprises a cut hypotube. In the embodiment illustrated in FIG.40B, the cut comprises a first helix 4002 having a first sense (e.g.,winding clockwise) and a second helix 4004 having the same first sense.The first helix 4002 is longitudinally offset from the second helix4004. In some embodiments, the cut pattern may comprise a variablehelix, which can vary flexibility longitudinally. In some embodiments,the hypotube may be embedded in a polymer. In some embodiments, thepolymer may have a durometer that varies longitudinally in longitudinalalignment with and/or longitudinally offset from helix variability.Other cut patterns are also possible. For example, the cut pattern maycomprise a single helix. For another example, the cut pattern maycomprise a plurality of transverse slots or kerfs connected by one ormore struts. In sine embodiments, a cut hypotube may provide tensilestrength.

FIG. 41A is a perspective view of an example of a catheter system 4100.The system 4100 comprises a proximal portion 4102 configured to remainout of the body of a subject and a distal portion 4104 configured to beinserted into vasculature of a subject. The distal portion 4104comprises a first expandable structure 4120 and a second expandablestructure 4122. The proximal portion comprises an actuation mechanism4112. The proximal portion 4102 is coupled to the distal portion 4104 bya catheter shaft 4106. In some embodiments, the catheter shaft isslightly rigid such that the catheter shaft 4106 can appose a sidewalland help to anchor the system 4100 at a target position. The proximalportion 4102 may comprise an adapter comprising a plurality of ports,for example the Y-adapter comprising a first Y-adapter port 4116 and asecond Y-adapter port 4118. The first Y-adapter port 4116 may be incommunication with a lumen in fluid communication with the secondexpandable member. The second Y-adapter port 4118 may be used to couplean electrode matrix of the system 4100 to a stimulator system 4119. Insome embodiments, the proximal portion 4102 comprises a stimulatorsystem 4119. For example, the proximal portion 4102 may compriseelectronics configured to provide stimulation to an electrode matrix,sensors (e.g., in communication with a fluid filled lumen of thecatheter shaft 4106), electronics to receive data from sensors,electronics for closed loop control, electronics to provide feedback toa user (e.g., physician, nurse, subject), input mechanisms for a user(e.g., physician, nurse, subject), etc.

FIG. 41B is a perspective view of a portion 4104 of the catheter system4100 of FIG. 41A in a collapsed and deflated state. FIG. 41C is atransverse cross-sectional side view of the portion 4104 of FIG. 41B.The illustrated distal portion 4104 includes part of the catheter shaft4106, the first expandable structure 4120, the second expandablestructure 4122, and a tubular member 4128. The first expandablestructure 4120 includes a plurality of splines coupled to the cathetershaft 4106. The tubular member 4128 may be in a lumen of the cathetershaft 4106. In some embodiments, the distal ends of the splines arecoupled to a distal hub that is coupled to the tubular member 4128, andthe proximal ends of the splines are coupled to the catheter shaft 4106.Distal segments of the splines may be slidable in a distal hub, forexample as described herein. The tubular member 4128 comprises a lumen4129. The lumen 4129 is in fluid communication with the secondexpandable member 4122.

The second expandable member 4122 may be adjacent to the firstexpandable member 4120 (e.g., distance of 0 cm) or longitudinally(proximally or distally) spaced from the first expandable member 4120 byup to about 5 cm (e.g., about 0.25 cm, about 0.5 cm, about 1 cm, about1.5 cm, about 2 cm, about 2.5 cm, about 3 cm, about 4 cm, about 5 cm,ranges between such values, etc.). The amount of spacing, if any, may atleast partially depend on the location of a target site, the stiffnessof the catheter shaft 4106, the number of splines of the firstexpandable member 4120, the expanded diameter of the first expandablemember 4120, etc.

FIG. 41D is a side view of the portion of 4104 of FIG. 41B in aninflated state. Specifically, the second expandable member 4122 isinflated. In some embodiments, fluid (e.g., saline, contrast, etc.) maybe injected into the lumen 4129 until the second expandable member 4122radially expands. In some embodiments, the second expandable member 4122may longitudinally expand. The inflated second expandable member 4122may be a Swan-Ganz balloon, which can be used to float the distalportion 4104 to a target site such as a pulmonary artery. Rather thantracking a guidewire through the catheter system 4100, the cathetersystem 4100 may comprise an all-in-one system in which the secondexpandable member comprises an electrode matrix. In some embodiments,the catheter system 4100 may be devoid of a second expandable member4122 and/or may be configured to track over a guidewire, which may bepositioned in vasculature (e.g., in the right pulmonary artery 4143)prior to introduction of the catheter system 4100, for example asdescribed herein using a Swan-Ganz technique, fluoroscopy-guidedsteering, etc.

FIG. 41E is a perspective view of the portion of 4104 of FIG. 41B in anexpanded state. Specifically, the first expandable member 4120 isexpanded. In some embodiments, operation of the actuation mechanism 4112can cause the first expandable structure 4120 to expand and contract.For example, rotation and/or longitudinal movement of the actuationmechanism 4112 can cause the tubular member 4128 to proximally retract,the catheter shaft 4106 to distally advance, or a combination thereof,each of which can push the first expandable member 4120 radiallyoutward. In certain such embodiments, the tubular member 4128 caninflate the second expandable member by flowing fluid through the lumen4129 and can expand the first expandable member 4120 by proximallyretracting. A dual function tubular member 4128 may reduce mass and/orcomplexity of the catheter system 4100. In some embodiments, differentstructures can be used to accomplish one or more of these functions. Forexample, in some embodiments, the splines may be self-expanding suchthat the actuation mechanism 4112 or another mechanism (e.g., retractionof a sheath over the splines) allows the splines to self-expand from acompressed state for navigation to a target site to an expanded statefor treatment at the target site. In certain such embodiments, thediameter of the first expandable structure 4120 in the expanded statemay be oversized to most the intended vasculature of most subjects toensure vessel wall apposition. In some embodiments, the splines may benon-self-expanding such that the splines only expand upon operation ofthe actuation mechanism 4112. In some embodiments, the splines may beself-expanding, and the actuation mechanism 4112 may further expand thesplines, which may provide an adjustable first expandable structure 4120diameter usable for a range of vessel sizes, wall apposition forces,etc. Embodiments in which the first expandable structure 4120 does notappose the wall in the event of an error could be advantageous forsafety, for example as described with respect to the system 2200. Insome embodiments, the wires are not fixed distally (e.g., to a distalhub), which can allow each wire to move independently, which mayaccommodate curvature at a deployment site.

In the expanded state, the first expandable structure 4120 comprisessplines that are circumferentially spaced from each other on one side ofa plane that includes a longitudinal axis of the distal portion 4104. Insome embodiments, the splines comprise wires having a diameter betweenabout 0.006 inches (approx. 0.15 mm) and about 0.015 inches (approx.0.38 mm) (e.g., about 0.006 inches (approx. 0.15 mm), about 0.008 inches(approx. 0.2 mm), about 0.01 inches (approx. 0.25 mm), about 0.012inches (approx. 0.3 mm), about 0.015 inches (approx. 0.38 mm), rangesbetween such values, etc.). In some embodiments, the diameter of theexpandable structure 4120 in the expanded state is between about 15 mmand about 30 mm (e.g., about 15 mm, about 20 mm, about 22 mm, about 24mm, about 26 mm, about 28 mm, about 30 mm, ranges between such values,etc.).

The splines of the first expandable member 4120 may comprise anelectrode array comprising a plurality of electrodes to form anelectrode matrix. The number of electrodes in the electrode matrix,electrode sizing, electrode spacing, etc. may be in accordance withother systems described herein. For example, in some embodiments, theexpandable structure 4120 comprises a mesh or membrane comprisingelectrodes that is stretched across two or more of the splines. Uponexpansion of the first expandable structure 4120, the electrodes of theelectrode matrix may be selectively activated for testing nerve capture,calibration, and/or therapy, for example as described herein.

FIG. 41F schematically illustrates the first expandable structure 4120expanded in vasculature. The vasculature may include, for example, apulmonary trunk 4132, a right pulmonary artery 4134, and a leftpulmonary artery 4136. In some embodiments, the catheter 4106 isasymmetric such that the catheter shaft 4106 can bend during floating tonaturally align the first expandable structure 4120 with the rightpulmonary artery 4134. After expansion of the first expandable structure4120, the catheter system 4100 may be proximally retracted until thefirst expandable structure 4120 snaps into place. Upon positioning ofthe first expandable member 4120, electrodes on splines of the firstexpandable structure 4120 may be used to stimulate a target nerve 4138.

FIG. 41G schematically illustrates another example of the firstexpandable structure 4120 expanded in vasculature. The vasculature mayinclude, for example, a pulmonary trunk 4132, a right pulmonary artery4134, and a left pulmonary artery 4136. The bending and positioning ofthe tubular member 4128 against the left side of the pulmonary trunk4132 may position and anchor the first expandable structure 4120 in theright pulmonary artery 4134 in a position for stimulating a target nerve4138.

In some embodiments, expansion of the first expandable structure 4120bends the distal portion 4104 relative to the catheter shaft 4106. Thisbending may advantageously help to anchor the distal portion 4104 at atarget site. For example, the tubular member 4128 can appose a firstside of a vessel and the catheter shaft 4106 can appose an opposite sideof the vessel.

FIG. 42A is a side view of an example of an electrode structure 4224.The electrode structure 4224 may be used with expandable structures asdescribed herein. In FIG. 42A, the electrode structure 4224 is shown ona spline 4222 of an expandable structure. The electrode structure 4224comprises a plurality of electrodes 4202 and insulation 4204 around theelectrodes 4202. The electrodes 4202 extend around the circumference ofthe electrode structure 4224. The electrode structure 4224 may be formedseparately and then slid over the spline 4222.

FIG. 42B is a side view of another example of an electrode structure4225. The electrode structure 4225 may be used with expandablestructures as described herein. In FIG. 42B, the electrode structure4225 is shown on a spline 4222 of an expandable structure. The electrodestructure 4225 comprises a plurality of electrodes 4203 and insulation4204 around the electrodes 4203. The electrodes 4203 extend partiallyaround the circumference of the electrode structure 4225. The electrodestructure 4225 further comprises insulation 4205 on an inner side, whichcan insulate the electrodes 4203 and direct energy radially outward. Theelectrode structure 4225 may be formed separately and then slid over thespline 4222.

FIG. 43A is a side view of an example of an electrode 4302. Theelectrode 4302 is a button electrode that may be coupled to a spline ora mesh. The electrode 4302 does not comprise insulation such that energymay be emitted in all directions.

FIG. 43B is a side view of another example of an electrode 4303. Theelectrode 4303 is a button electrode that may be coupled to a spline ora mesh. The electrode 4303 comprises insulation 4305 such that energy isemitted from uninsulated areas, which can provide directional control.

FIG. 44A is a side view of an example of an electrode 4402. Theelectrode 4402 is a barrel electrode that may be coupled to a spline ora mesh. The electrode 4303 does not comprise insulation such that energymay be emitted in all directions.

FIG. 44B is a side view of another example of an electrode 4403. Theelectrode 4403 is a barrel electrode that may be coupled to a spline ora mesh. The electrode 4403 comprises insulation 4405 such that energy isemitted from uninsulated areas, which can provide directional control.In some embodiments, the rotational position of the electrode 4403around a spline is fixed, for example to direct energy radially outward.

FIG. 45 is a schematic diagram of neurostimulation of a nerve proximateto a vessel wall. An electrode 4508 is positioned in a vessel cavity4506, and the vessel wall 4504 is proximate to or adjacent to a nerve4502. The electrode 4508 is partially insulated (e.g., as in theelectrode 4303) such that energy primarily radiates from one side. Theelectrode 4508 may have an area between about 1 mm² and about 3 mm². Insome embodiments, the electrode 4508 comprises platinum iridium. In someembodiments, the uninsulated surface of the electrode 4508 is treated,for example to increase surface area. The energy radiates from thesurface of the electrode 4508 and dissipates in the vessel wall 4504. Aportion of the energy radiates out of the vessel wall 4504 and capturespart of the nerve 4502. The nerve 4502 also dissipates the energy, whichdoes not extend far beyond the nerve 4502, which could reduce thechances of capturing other undesired or unintended nerves, which couldreduce side effects such as pain, cough, etc. The nerve may have adiameter 4503 between about 1 mm and about 2 mm. Even with insulation,some energy may be emitted from the opposite surface into the vesselcavity 4506, where blood or other materials may dissipate the energy.

Table 1 shows the correlation between changes in right ventriclecontractility and left ventricle contractility after three differentchanges. The correlation was a heartbeat-by-heartbeat analysis. Pressuremeasurements, taken by a Millar catheter comprising a MEMS pressuresensor, in units of max(dP/dt) was used as a surrogate forcontractility.

The first change, a dobutamine injection, provided a very highcontractility increase greater than 500%. The average correlationbetween right ventricle contractility and left ventricle contractilitywas very good at 0.91, where 1.00 is a perfect correlation. Accordingly,if a subject is given a dobutamine injection, measuring changes to rightventricle contractility can provide accurate information about changesto left ventricle contractility. The first change was repeated threetimes.

The second change, calcium injection at 5 mL, provided a contractilityincrease of about 20%. FIG. 46A shows the left ventricle pressure inblue as measured by a Millar Mikro-Cath (MEMS) pressure sensor catheter,right ventricle pressure as measured by a pressure sensor incommunication with a fluid filled lumen in yellow, and right ventriclepressure in purple as measured by a Millar Mikro-Cath (MEMS) pressuresensor catheter, as well as arterial pressure in green as measured inthe aorta by a Millar Mikro-Cath (MEMS) pressure sensor catheter. Theaverage correlation between right ventricle contractility and leftventricle contractility using a Millar (MEMS) sensor on a catheter wasvery good at 0.91. The average correlation between right ventriclecontractility and left ventricle contractility using a fluid-filledlumen of a Swan-Ganz catheter in communication with an external pressuresensor was also very good at 0.87. Accordingly, under certaincircumstances such as measurement of an animal (normal, non-HF ovinemodel) model, if a subject is given a calcium injection, measuringchanges to right ventricle contractility with a MEMS sensor or a fluidfilled lumen can provide accurate information about changes to leftventricle contractility.

The fourth change, neurostimulation as described herein, provided acontractility increase of about 28%. The correlation between rightventricle contractility and left ventricle contractility was very goodat 0.90. Accordingly, if a subject is given neurostimulation, measuringchanges to right ventricle contractility can provide accurateinformation about changes to left ventricle contractility. FIG. 46Bshows the left ventricle contractility in teal and the right ventriclecontractility in gold for the neurostimulation change in which theneurostimulation was applied after about 35 seconds and then cut offafter being applied for about 2 minutes. In the first several beatsafter the calcium injection, the left ventricle contractility increaseddramatically, but the right ventricle contractility only slightlyincreased. Thereafter, the left ventricle contractility tapered offlogarithmically or exponentially, but the right ventricle contractilitydecreased very slowly. These differences help to show why thecorrelation between left ventricle contractility and right ventriclecontractility are poorly correlated for calcium injections. The fourthchange was not repeated.

TABLE 1 Change Average R-Value Contractility % Increase DobutamineInjection 0.91 >500 Calcium Injection 0.91 ~20 (5 mL) (Millar) 0.87(Fluid Filled) Neurostimulation 0.90 ~28

In some embodiments, a MEMS pressure sensor can be integrated into thecatheter systems described herein, for example configured to reside inthe right ventricle to measure right ventricle contractility, which canbe accurately correlated to left ventricle contractility forneurostimulation. In some embodiments, an alternative pressuremeasurement system, for example a fluid-filled (e.g., saline-filled)lumen having a first end in communication with an external pressuresensor (e.g., connected via a luer fitting) and a second end incommunication with an aperture configured to reside in the rightventricle to measure right ventricle contractility, which can beaccurately correlated to left ventricle contractility forneurostimulation. MEMS pressure sensors may provide higher fidelity(more immediate feedback) than pressure sensing lumens. MEMS pressuresensors may occupy less catheter volume because they do not include alumen, which can reduce the size of the catheter and/or provideadditional space for other devices. MEMS pressure sensors may be easierto set up, for example compared to filling a lumen with fluid andcorrectly coupling the fluid filled lumen to a sensor. MEMS pressuresensors may be easier to place anatomically. Easier set up and/orplacement may lead to more accurate results. MEMS pressure sensors mayreduce or eliminate a whip effect in which curvature of a fluid filledlumen may kink when bending around a curve, which can provide inaccuratereadings. Pressure sensing lumens may advantageously be well suited forlong dwell times, as they are less likely to be affected by blood thanMEMS sensors. In some embodiments, multiple pressure sensors, of thesame type or different types, may be used, for example to provide a moreaccurate measurement (e.g., by taking an average or a weighted averageof the measurements).

The accuracy of measurement of left ventricle contractility by measuringright ventricle contractility during neurostimulation can be used tomonitor therapy efficacy. The accuracy of measurement of left ventriclecontractility by measuring right ventricle contractility duringneurostimulation can be used to monitor therapy efficacy. In someembodiments, left ventricle contractility, after correlation from ameasurement of right ventricle contractility, can be used for closedloop control (e.g., neurostimulation parameter adjustments, turningneurostimulation on and/or off, etc.).

In some embodiments, pressure such as right ventricle pressure can bemonitored for safety purposes. For example, right ventricle pressure,correlated left ventricle pressure, and optionally other measurementssuch as right atrium pressure can be used as a surrogate ECG signal fordetermining heart rate and/or arrhythmias. As described below, suchvariables may not be normally measurable during stimulation.

For another example, pressure can be used to determine if a catheter hasmoved, for example from the right ventricle into the right atrium or thesuperior vena cava, or from the pulmonary artery into the rightventricle. The system may be configured to trigger (e.g., automatically)certain events upon determination of movement, such as stoppingstimulation, collapsing an electrode basket, releasing an anchor, etc.

FIG. 47A schematically illustrates an example electrocardiograph (ECG orEKG). The ECG includes a P wave, a Q wave, a R wave, a S wave, and a Twave, which are indicative of different events during a single heartbeatof a healthy patient. The P wave represent atrial depolarization, whichcauses the left atrium and the right atrium to push blood into the leftventricle and right ventricle, respectively. The flat period until the Qwave, the “PR Segment,” and the start of the P wave to the start of theQ wave is the “PR Interval.” The Q wave, the R wave, and the S wave,together the “QRS Complex,” represent ventricular depolarization, whichcauses the right ventricle to push blood into the pulmonary artery andtowards the lungs and which causes the left ventricle to push blood intothe atrium for distribution to the body. The T wave representsrepolarization of the left and right ventricles. The flat period untilthe T wave is the “ST Segment” during which the ventricles aredepolarized, and collectively the QRS Complex, the ST Segment, and the Twave are the “QT Interval.” Some ECGs also have a U wave after the Twave. The timing, amplitude, relative amplitude, etc. of the variouswaves, segments, intervals, and complexes can be used to diagnosevarious conditions of the heart. Electrical stimulation from the systemsdescribed herein may interfere with a normal ECG. In some embodiments,the ECG signal may be modified to account for such interference.

In some embodiments, the ECG may be monitored by the system so thatstimulation is only applied during, for example, the period between theT wave and the P wave, the period between the S wave and the P wave, theperiod between the S wave and the Q wave, etc. The ECG may beartificially flatlined during periods of stimulation but unaffectedduring periods of non-stimulation. Some users may prefer to see aflatline or “blank” period rather than noise, an artificial signal, etc.In some embodiments, the ECG may be flatlined artificially high or lowor show an irregular pattern during periods of stimulation so that auser of the ECG recognizes that the signal during such periods is notaccurate. FIG. 47B is an example of a modified electrocardiograph.During stimulation, which occurs in the period between the S wave andthe T wave, the ECG is artificially low.

FIG. 47C is an example of a monitored electrocardiograph. As discussedabove, the stimulation is timed to heartbeats. Rather than relying onthe heartbeat, including intrabeat duration, remaining regular,stimulation is applied for a portion of the time between heartbeats,after which the ECG is monitored for the next beat. For example,stimulation is applied for a short period after S wave (represented by“S” in FIG. 47C), followed by a monitoring period where the P waveshould begin or be completed (represented by “M” in FIG. 47C). If the Pwave is detected, then stimulation and monitoring are repeated. If the Pwave is not detected in the monitoring period, which may be indicativethat something is wrong, stimulation can be stopped. Stimulation may berestarted by a user after determining that conditions are appropriatefor stimulation. Stimulation may be restarted automatically by thesystem after a certain number of normal heartbeats following theaberration.

In some embodiments, for example in which the stimulation system has alow duty cycle such as 1 second ON and 5 seconds OFF, 5 seconds ON and10 seconds OFF, etc., the ECG may be halted during the period ofstimulation and replaced with an alternative reading.

FIG. 47D is an example of a modified electrocardiograph. Duringstimulation, the entire electrocardiograph is flatlined. In someembodiments, the ECG may be flatlined artificially high or low so that auser of the ECG recognizes that the signal during such periods is notaccurate.

FIG. 47E is another example of a modified electrocardiograph. Duringstimulation, the duration of which is known in advance, theelectrocardiograph from the period preceding the stimulation is copiedand presented again as the ECG during stimulation. FIG. 47F is stillanother example of a modified electrocardiograph. During stimulation, anartificial ECG, for example based on other patient data such aspressure, a perfect ECG, etc., is presented as the ECG duringstimulation. In some embodiments based on pressure data, the artificialportion of the ECG may comprise or alternatively consist essentially ofa R wave indicative of left ventricle contraction. The modified ECG ofFIGS. 47E and 47F may allow integration with other machinery, forexample which might alarm or function improperly if an ECG varied from anormal ECG.

FIG. 47G is yet another example of a modified electrocardiograph. Duringstimulation, an artificial ECG that is known to be artificial byvisualization. For example, rather than waves with peaks, the waves maybe represented as square waves. The modified ECG of FIG. 47G may allowintegration with other machinery, for example which might alarm orfunction improperly if an ECG varied from a normal ECG, and/or can bevisualized and clearly known to not be representative of actual ECGdata.

In some embodiments, the effect of the stimulation on the ECG can befiltered out to present a true ECG during periods of stimulation.

Certain safety systems for the catheter systems are described herein,for example collapsing to a retracted state. In some embodiments, aparameter may be monitored, and certain events can be effected inresponse to a monitored parameter exceeding a threshold.

In some embodiments, the monitored parameter comprises pressure from apressure sensor configured to be in the pulmonary artery. A pressuredeviating from pulmonary artery pressure may indicate that the catheterhas slid back such that electrodes may be in the right ventricle. Eventsthat may be effected include stopping stimulation, collapsing anexpandable member, and/or sounding an alarm. In some embodiments, rightventricle pressure may be monitored to confirm that the deviatingpressure shows right ventricle pressure. Other combinations of sensorpositions and vascular pressures, for example between a downstreamcavity and an upstream cavity, are also possible. For example, rightpulmonary artery to pulmonary artery, left pulmonary artery to pulmonaryartery, pulmonary artery to right ventricle, right ventricle to rightatrium, right atrium to superior vena cava, right atrium to inferiorvena cava, superior vena cava to left brachiocephalic vein, superiorvena cava to right brachiocephalic vein, left brachiocephalic vein toleft internal jugular vein, right brachiocephalic vein to right internaljugular vein, combinations thereof, and the like.

In some embodiments, the monitored parameter comprises movement from amovement sensor. The pressure sensor may comprise, for example, acapacitive sensor, a magnetic sensor, a contact switch, combinationsthereof, and the like. In some embodiments, the movement sensor ispositioned at the access point (e.g., a left internal jugular vein).Movement greater than a certain distance (e.g., greater than about 0.5cm, greater than about 1 cm, or greater than about 2 cm) may triggereffect events including stopping stimulation, collapsing an expandablemember, and/or sounding an alarm. In some embodiments, a plurality ofmovement sensors spaced longitudinally along the system may be used toverify the detected movement.

In some embodiments, the monitored parameter comprises heart rate. Asdescribed herein, a pressure waveform may be used to monitor heart rateduring stimulation. Other methods of monitoring heart rate duringstimulation are also possible. If the heart rate changes by a certainamount or percentage, events that may be effected include stoppingstimulation, collapsing an expandable member, and/or sounding an alarm.

In some embodiments, the monitored parameter comprises electrodeimpedance. If an electrode is configured to be pressed against a vesselwall, or spaced from the vessel wall by a distance, that configurationresults in an impedance. If the impedance changes by a certain amount orpercentage, events that may be effected include stopping stimulation,collapsing an expandable member, using an unused electrode, and/orsounding an alarm.

The catheter systems disclosed herein can be delivered, deployed,operated, and removed from the body according to any suitable method.FIGS. 48A-48H illustrate an example method for delivering and deployinga catheter system 4800 comprising an expandable structure 4820 includingelectrodes 4824. The catheter system 4800 may be the same or similar tothe catheter system 3700 or other catheter systems disclosed herein. Thecatheter system 4800 may be delivered through a jugular vein to thesuperior vena cava, right atrium, right ventricle, through the pulmonaryvalve, and into the right pulmonary artery.

As shown in FIG. 48A, a syringe 4813 may be used to insert a needle 4814for initially accessing the jugular vein 4815. A guidewire 4816 may thenbe inserted into the jugular vein 4815 through the needle 4814. As shownin FIG. 48B, the needle 4814 may be removed, and an introducer 4830 maybe inserted into the jugular vein 4815 over the guidewire 4816, suchthat the introducer 4830 spans and maintains the opening into thejugular vein 4815. The introducer may comprise, for example, 11 FrenchARROW-FLEX® introducer from Teleflex, Inc. of Westmeath, Ireland,although other introducers may be used. The introducer may comprise aflexible shaft 4831 and a hemostasis valve 4832.

After the introducer 4830 is inserted into the jugular vein 4815, aSwan-Ganz catheter 4840 may be floated to the right pulmonary artery4842, as illustrated in FIG. 48C. The Swan-Ganz catheter 4840 comprisesan inflatable balloon 4841 at its distal end. The Swan-Ganz catheter4842 may be inserted into the introducer 4830 over the guidewire 4816,and, once the balloon 4841 is distal to the introducer 4830, the balloon4841 may be inflated. The inflated balloon 4841 is carried by thenatural blood flow, pulling the distal tip of the Swan-Ganz catheter4840 into the right pulmonary artery 4842. The guidewire 4816 may bedistally advanced through a guidewire lumen of the Swan-Ganz catheter4840 until the distal end of the guidewire 4816 is positioned in theright pulmonary artery 4842. Once the guidewire 4816 is in place, theballoon 4841 may be deflated and the Swan Ganz catheter 4840 can beproximally retracted out of the vasculature. The catheter assembly 4800may include an inflatable balloon at its distal end such that the SwanGanz catheter 4840 and the guidewire 4816 may be omitted.

An introducer sheath 4833 and dilator 4834 can be tracked over theguidewire 4816 to the pulmonary trunk or the right pulmonary artery4842. When the introducer sheath 4833 is in place, the dilator 4834 canbe withdrawn. The catheter system 4800 may be inserted through theintroducer 4830, through the introducer sheath 4833, and tracked overthe guidewire 4816 to the distal end of the introducer sheath 4833. Ifthe expandable structure 4820 is self-expanding the expandable structurecan be in a radially compressed state in the introducer sheath 4833 andin a radially expanded state out of the introducer sheath 4833. Theexpandable structure 4820 may prolapse from the distal end of theintroducer sheath 4833 by distally advancing the expandable structure,proximally retracting the introducer sheath 4833, and/or combinationsthereof. For example, if the distal end of the introducer sheath 4833 isin the pulmonary trunk, the expandable structure 4820 may be distallyadvanced and follow the guidewire 4816 into the right pulmonary artery4842. FIG. 48D shows the expandable structure 4820 in a radiallyexpanded configuration after exiting the distal end of the introducersheath 4833.

The introducer sheath 4833 may be retracted to a position proximal ordistal to the pulmonary valve 4847. If the catheter system 4800 includesa pressure sensor positioned in the right ventricle 4849, the distal endof the introducer sheath 4833 may be retracted to a position proximal tothe pressure sensor, and thus proximal to the pulmonary valve 4847, toexpose the pressure sensor to the right ventricle. The introducer sheath4833 may be retracted to a position distal to the pulmonary artery 4847such that proximal retraction of the expandable member 4820 causes theexpandable member 4820 to be radially compressed by the introducersheath 4833 and an expanded expandable member 4820 cannot cross thepulmonary valve 4847. If the introducer sheath 4833 is splittable, theintroducer 4830 may be retracted from the body entirely and removed fromthe catheter shaft assembly 4806 by splitting along its circumference.

FIGS. 48D-48E show the expandable structure 4820 positioned within theright pulmonary artery 4842. In FIG. 48D, is in a self-expanded stateafter exiting the distal end of the introducer sheath 4833. In FIG. 48E,the expandable structure 4820 is in a further expanded state, forexample due to retraction of an actuation tube. As seen in FIGS.48D-48E, the durometer of the flexible tubing and/or the hinge of thecatheter shaft assembly 4806 can allow a tight bend (approximately 90degrees) as the catheter system 3800 transitions from the pulmonaryartery trunk into the right pulmonary artery 4842. The catheter shaftassembly 4806 may be positioned firmly against the left side of thepulmonary artery trunk. Upon further expansion, for example 2 mm greaterthan the diameter of the right pulmonary artery 4842 in a maximumsystolic state, the expandable structure 4820 is anchored. Theneuromodulation procedure may occur over several days, so maintaining aposition of the expandable structure 4820 by anchoring in the rightpulmonary artery 4842 may provide consistency over the duration of theprocedure.

The introducer 4830 may optionally be fixed relative to the patientduring the procedure to inhibit or prevent inadvertent repositioning ofthe catheter system 4800. FIG. 48F shows an example of a handle 4810 ofa catheter assembly 4800 that has been inserted into an introducer 4830.A silicone sleeve may be placed over the introducer 4830 and sutured toa surface outside the body of the patient and/or directly sutured to thepatient. In some embodiments, the introducer 4830 is about 65 cm longand the catheter shaft assembly 4806 is about 100 cm long, leaving about35 cm of neck 4835. After the introducer sheath 4833 is partiallyretracted, for example proximal to the pulmonary valve 4847, the neck4835 may be reduce to about 15 to 20 cm. The introducer valve 4832 mayform a secure connection between the introducer 4830 and the cathetershaft assembly 4806 of catheter system 4800, such that the cathetersystem 4800 is not easily moved relative to the introducer 4830. Asilicone sleeve can optionally be placed over the actuation shaftassembly 4806 along the neck 4835 to maintain the desired spacing. Aninadvertent dislocation of the expandable structure 4820 may be detectedby a measured change in the heart contractility if the electrodes 4824are shifted out of a proper stimulating position.

The electrode array 4829 of the expandable structure 4820 may bepositioned toward the superior and posterior portion of the rightpulmonary artery 4842 for stimulating one or more cardiopulmonarynerves. Fluoroscopy may be used to visualize the positioning of thecatheter system 4800, including the expandable structure 4820, to ensureproper orientation is achieved, especially relating to thecircumferential orientation the electrode array 4829. Fluoroscopy may beperformed with or without contrast agents. FIG. 48G shows a fluoroscopicimage of the catheter system 4800 inserted into right pulmonary artery4842. The electrode array 4829 of expandable structure 4820 is visiblewithout use of a contrast agent. Navigational guidance systems whichincorporate positional sensors on catheters (e.g., NavX™, from St. JudeMedical Inc.) and/or cardiac mapping systems which map theelectrophysiology of the heart surface may be used in conjunction withfluoroscopy or alternatively to fluoroscopy. Mapping performedadditionally to fluoroscopy may be performed prior to or simultaneouslywith fluoroscopy. Pressure sensors or other means may be used to trackpositions of components of the catheter system, which can reduce oreliminate use of fluoroscopy.

FIG. 48H schematically depicts the activation of all of the electrodes4824 on a single spline for stimulating a target nerve 4843, althoughactual stimulation protocols may include as few as two electrodes 4824,include electrodes 4824 on different splines, etc. The target nerve 4843may be a cardiopulmonary nerve. In some embodiments, two electrodes 4824positioned on either side of the target nerve 4843 may be activated. Insome embodiments, the target nerve 4843 may be identified afterpositioning the expandable structure 4820 by “electrically moving” thecatheter system 4800, in which the catheter system 4800 and theexpandable structure 4820 are not physically repositioned, but theselection of “active” electrodes 4824 within the electrode array 4829 isshifted across the array 4829 or otherwise altered to better capture thetarget nerve 4843. The electrode array 4829 may be positioned so thatthe nerve is positioned between two or more electrodes (e.g., betweentwo electrodes, between three electrodes, between four electrodes,etc.).

In some embodiments, a voltage pre-pulse may be applied to the tissuesurrounding the target nerve 4843 immediately preceding a stimulationpulse. The pre-pulse may pre-polarize the nearby tissue and make iteasier to stimulate the target nerve 4843 while avoiding stimulation ofnearby pain nerves. For example, a stimulation protocol may include asmaller amplitude pulse with a first polarity (e.g., positive or anodicpolarity) configured to pre-polarize the tissue followed immediately oralmost immediately by a larger amplitude pulse of second polarity (e.g.,negative or cathodic) configured to stimulate the target nerve 4843. Thesecond polarity may be opposite the first polarity. The pre-pulse may beapplied by the same or different electrodes 4824 of the electrode array4829.

In some embodiments of use, the active electrodes which are to be usedduring the stimulation procedure are first identified by a fasttitration. During a fast titration, the patient may be sedated to avoidpain so that the electrodes 4824 may be selectively activated at fullpower to determine which electrode or electrodes 4824 best capture thetarget nerve 4843. After the fast titration, the selected activeelectrodes 4824 may be activated with a lower power and increased todetermine the optimal power setting for stimulating the target nerve4843, during which the patient need not be sedated.

The electrodes 4824 may be activated in a monopolar or bipolar (e.g.,guarded bipolar) fashion. Monopolar stimulation may use negative orpositive polarity and includes the use of a return conductor. The returnconductor may be at least 5 mm away from the electrodes. For example,the return conductor may be attached to or integrated with a portion ofthe catheter system 4800 or another catheter configured to be in theright ventricle 4849. For another example, the return conductor may beattached to or integrated with a portion of the catheter system 4800 oranother catheter configured to be in the superior vena cava. For yetanother example, the return conductor may be attached to or integratedwith a portion of the catheter system 4800 or another catheterconfigured to be in the brachiocephalic or innominate vein. The currentvector from the electrodes 4824 to the brachiocephalic vein may be awayfrom at least one of the heart and the trachea, which may reduce sideeffects and/or increase patient tolerance. In certain such embodiments,the jugular vein assessed may be the left jugular vein. The returnconductor may comprise a patch affixed to the skin.

Upon completion of the procedure, the catheter system 4800 may beremoved from the body according to any suitable method. The actuationmechanism of the handle 4810 of the catheter system 4800 can be releasedso that the expandable structure 4820 can be in a self-expanded, but notfurther expanded, state. The expandable structure 4820 may then enterthe introducer sheath 4833 by proximal retraction of the expandablemember, distal advancement of the introducer sheath 4833, or acombination thereof. The introducer sheath 4833 may be retracted fromthe body with the catheter system 4800 in tow. The expandable structure4820 may be retracted from the body through the introducer sheath 4833,and then the introducer sheath 4833 may be retracted.

The effectiveness of the neural stimulation on heart contractility,particularly of the left ventricle, can be monitored, for example, bymeasuring pressure within the heart. Pressure may be measured by apressure sensor such as a fluid-filled column, a MEMS sensor, or anothersuitable type of pressure sensor. The pressure sensor may be attached toor integrated with the catheter system 4800, for example, along thecatheter shaft assembly 4806. If the pressure sensor is attached to orintegrated with the catheter system 4800, the sensor may be positionedin the right ventricle. The pressure in the right ventricle may becorrelated to the pressure in the left ventricle, such that the leftventricular pressure and therefore left ventricle contractility may besufficiently approximated. A pressure sensor may alternatively beinserted into the heart through another catheter, and may be placed inthe right ventricle, in the left ventricle, or another suitablelocation. The left ventricular pressure may be used to optimize theeffect of the neural stimulation on heart contractility over the courseof the procedure. The heart contractility may be measurably increased,for example, by 5-12% during the procedure. A single catheter maycomprise a plurality of sensors. For example, one sensor may beconfigured as above and a second sensor may be configured to reside inthe right pulmonary artery. The sensor in the right pulmonary arterycould provide a wedge pressure, which is a reading known to users from aSwan Ganz catheterization procedure. A sensor in the right pulmonaryartery may be usable for safety. For example, if a pressure sensor inthe right pulmonary artery migrated below the pulmonary valve, thenstimulation could be shut off (e.g., immediately upon detection based ona change in pressure (e.g., percentage change or absolute change) and/oran absolute value of pressure (e.g., above or below a certain pressure))in order to inhibit or prevent cardiac arrhythmias.

The foregoing description and examples has been set forth merely toillustrate the disclosure and are not intended as being limiting. Eachof the disclosed aspects and embodiments of the present disclosure maybe considered individually or in combination with other aspects,embodiments, and variations of the disclosure. In addition, unlessotherwise specified, none of the steps of the methods of the presentdisclosure are confined to any particular order of performance.Modifications of the disclosed embodiments incorporating the spirit andsubstance of the disclosure may occur to persons skilled in the art andsuch modifications are within the scope of the present disclosure.Furthermore, all references cited herein are incorporated by referencein their entirety.

While the methods and devices described herein may be susceptible tovarious modifications and alternative forms, specific examples thereofhave been shown in the drawings and are herein described in detail. Itshould be understood, however, that the invention is not to be limitedto the particular forms or methods disclosed, but, to the contrary, theinvention is to cover all modifications, equivalents, and alternativesfalling within the spirit and scope of the various embodiments describedand the appended claims. Further, the disclosure herein of anyparticular feature, aspect, method, property, characteristic, quality,attribute, element, or the like in connection with an embodiment can beused in all other embodiments set forth herein. Any methods disclosedherein need not be performed in the order recited. Depending on theembodiment, one or more acts, events, or functions of any of thealgorithms, methods, or processes described herein can be performed in adifferent sequence, can be added, merged, or left out altogether (e.g.,not all described acts or events are necessary for the practice of thealgorithm). In some embodiments, acts or events can be performedconcurrently, e.g., through multi-threaded processing, interruptprocessing, or multiple processors or processor cores or on otherparallel architectures, rather than sequentially. Further, no element,feature, block, or step, or group of elements, features, blocks, orsteps, are necessary or indispensable to each embodiment. Additionally,all possible combinations, subcombinations, and rearrangements ofsystems, methods, features, elements, modules, blocks, and so forth arewithin the scope of this disclosure. The use of sequential, ortime-ordered language, such as “then,” “next,” “after,” “subsequently,”and the like, unless specifically stated otherwise, or otherwiseunderstood within the context as used, is generally intended tofacilitate the flow of the text and is not intended to limit thesequence of operations performed. Thus, some embodiments may beperformed using the sequence of operations described herein, while otherembodiments may be performed following a different sequence ofoperations.

The various illustrative logical blocks, modules, processes, methods,and algorithms described in connection with the embodiments disclosedherein can be implemented as electronic hardware, computer software, orcombinations of both. To clearly illustrate this interchangeability ofhardware and software, various illustrative components, blocks, modules,operations, and steps have been described above generally in terms oftheir functionality. Whether such functionality is implemented ashardware or software depends upon the particular application and designconstraints imposed on the overall system. The described functionalitycan be implemented in varying ways for each particular application, butsuch implementation decisions should not be interpreted as causing adeparture from the scope of the disclosure.

The various illustrative logical blocks and modules described inconnection with the embodiments disclosed herein can be implemented orperformed by a machine, such as a general purpose processor, a digitalsignal processor (DSP), an application specific integrated circuit(ASIC), a field programmable gate array (FPGA) or other programmablelogic device, discrete gate or transistor logic, discrete hardwarecomponents, or any combination thereof designed to perform the functionsdescribed herein. A general purpose processor can be a microprocessor,but in the alternative, the processor can be a controller,microcontroller, or state machine, combinations of the same, or thelike. A processor can also be implemented as a combination of computingdevices, e.g., a combination of a DSP and a microprocessor, a pluralityof microprocessors, one or more microprocessors in conjunction with aDSP core, or any other such configuration.

The blocks, operations, or steps of a method, process, or algorithmdescribed in connection with the embodiments disclosed herein can beembodied directly in hardware, in a software module executed by aprocessor, or in a combination of the two. A software module can residein RAM memory, flash memory, ROM memory, EPROM memory, EEPROM memory,registers, hard disk, a removable disk, an optical disc (e.g., CD-ROM orDVD), or any other form of volatile or non-volatile computer-readablestorage medium known in the art. A storage medium can be coupled to theprocessor such that the processor can read information from, and writeinformation to, the storage medium. In the alternative, the storagemedium can be integral to the processor. The processor and the storagemedium can reside in an ASIC. The ASIC can reside in a user terminal. Inthe alternative, the processor and the storage medium can reside asdiscrete components in a user terminal.

Conditional language used herein, such as, among others, “can,” “might,”“may,” “e.g.,” and the like, unless specifically stated otherwise, orotherwise understood within the context as used, is generally intendedto convey that some embodiments include, while other embodiments do notinclude, certain features, elements, and/or states. Thus, suchconditional language is not generally intended to imply that features,elements, blocks, and/or states are in any way required for one or moreembodiments or that one or more embodiments necessarily include logicfor deciding, with or without author input or prompting, whether thesefeatures, elements and/or states are included or are to be performed inany particular embodiment.

The methods disclosed herein may include certain actions taken by apractitioner; however, the methods can also include any third-partyinstruction of those actions, either expressly or by implication. Forexample, actions such as “positioning an electrode” include “instructingpositioning of an electrode.”

The ranges disclosed herein also encompass any and all overlap,sub-ranges, and combinations thereof. Language such as “up to,” “atleast,” “greater than,” “less than,” “between,” and the like includesthe number recited. Numbers preceded by a term such as “about” or“approximately” include the recited numbers and should be interpretedbased on the circumstances (e.g., as accurate as reasonably possibleunder the circumstances, for example ±5%, ±10%, ±15%, etc.). Forexample, “about 1 V” includes “1 V.” Phrases preceded by a term such as“substantially” include the recited phrase and should be interpretedbased on the circumstances (e.g., as much as reasonably possible underthe circumstances). For example, “substantially perpendicular” includes“perpendicular.” Unless stated otherwise, all measurements are atstandard conditions including temperature and pressure.

What is claimed is:
 1. A method of reducing a duty cycle during aneurostimulation treatment period while maintaining an efficacioustherapeutic effect, the method comprising: during a first sequence,alternatingly: applying a neurostimulation to a nerve in a chest cavityin an ON state for a first duration; and stopping application of theneurostimulation in an OFF state for a second duration, the secondduration being twice as long as the first duration; during a secondsequence after the first sequence and during which no neurostimulationis applied; monitoring a physiologic signal; and storing apost-stimulation level of the physiologic signal; during a thirdsequence after the second sequence, monitoring the physiologic signalfor deviation from the post-stimulation level by a threshold value; andupon detecting the deviation greater than the threshold value,alternatingly applying the neurostimulation and stopping applying theneurostimulation until the deviation is less than the threshold value.2. The method of claim 1, wherein the efficacious therapeutic effectcomprises increasing cardiac contractility.
 3. The method of claim 1,wherein applying the neurostimulation during the first sequence is untilachieving a steady state of the physiologic signal.
 4. The method ofclaim 1, wherein a parameter of the ON state increases from an initialvalue to a final value during the first sequence, wherein the parametercomprises at least one of amplitude, pulse width, or frequency.
 5. Themethod of claim 1, wherein the physiologic signal decays during thesecond sequence, and wherein the method comprises reducing the decay. 6.The method of claim 1, wherein applying the neurostimulation during thefirst sequence is until achieving a steady state of the physiologicsignal, wherein a parameter of the ON state increases from an initialvalue to a final value during the first sequence, wherein the parametercomprises at least one of amplitude, pulse width, or frequency, andwherein the physiologic signal decays during the second sequence, andwherein the method comprises reducing the decay.
 7. A method of reducinga duty cycle during a neurostimulation treatment period whilemaintaining an efficacious therapeutic effect, the method comprising:during a first sequence, alternatingly: applying a neurostimulation to anerve in an ON state for a first duration; and stopping application ofthe neurostimulation in an OFF state for a second duration, the secondduration being longer than the first duration; during a second sequenceafter the first sequence and during which no neurostimulation isapplied; monitoring a physiologic signal; and storing a post-stimulationlevel of the physiologic signal; during a third sequence after thesecond sequence, monitoring the physiologic signal for deviation fromthe post-stimulation level by a threshold value; and upon detecting thedeviation greater than the threshold value, alternatingly applying theneurostimulation and stopping applying the neurostimulation until thedeviation is less than the threshold value.
 8. The method of claim 7,wherein the efficacious therapeutic effect comprises increasing cardiaccontractility.
 9. The method of claim 7, wherein applying theneurostimulation during the first sequence is until achieving a steadystate of the physiologic signal.
 10. The method of claim 7, wherein aparameter of the ON state increases from an initial value to a finalvalue during the first sequence.
 11. The method of claim 10, wherein theparameter comprises at least one of amplitude, pulse width, orfrequency.
 12. The method of claim 7, wherein the physiologic signaldecays during the second sequence, and wherein the method comprisesreducing the decay.
 13. The method of claim 7, wherein applying theneurostimulation during the first sequence is until achieving a steadystate of the physiologic signal, wherein a parameter of the ON stateincreases from an initial value to a final value during the firstsequence, wherein the parameter comprises at least one of amplitude,pulse width, or frequency, and wherein the physiologic signal decaysduring the second sequence, and wherein the method comprises reducingthe decay.
 14. A method of reducing a duty cycle during aneurostimulation treatment period while maintaining an efficacioustherapeutic effect, the method comprising: during a first sequence,alternatingly: applying a neurostimulation to a nerve in an ON state fora first duration; and stopping application of the neurostimulation in anOFF state for a second duration, the second duration being longer thanthe first duration; after the first sequence: monitoring a physiologicsignal; storing a level of the physiologic signal; continue monitoringthe physiologic signal for deviation from the level; and upon detectingthe deviation in the physiologic signal, alternatingly: applying theneurostimulation to the nerve in the ON state for the first duration;and stopping application of the neurostimulation in the OFF state forthe second duration, the second duration being longer than the firstduration.
 15. The method of claim 14, wherein the efficacioustherapeutic effect comprises increasing cardiac contractility.
 16. Themethod of claim 14, wherein applying the neurostimulation during thefirst sequence is until achieving a steady state of the physiologicsignal.
 17. The method of claim 14, wherein a parameter of the ON stateincreases from an initial value to a final value during the firstsequence.
 18. The method of claim 17, wherein the parameter comprises atleast one of amplitude, pulse width, or frequency.
 19. The method ofclaim 14, wherein the physiologic signal decays during the secondsequence, and wherein the method comprises reducing the decay.
 20. Themethod of claim 14, wherein applying the neurostimulation during thefirst sequence is until achieving a steady state of the physiologicsignal, wherein a parameter of the ON state increases from an initialvalue to a final value during the first sequence, and wherein theparameter comprises at least one of amplitude, pulse width, orfrequency.